BRAF Mutations in Thyroid Cancer

by Jason Wasserman MD PhD FRCPC
March 30, 2026

If your pathology report or molecular test results mention a BRAF mutation — most commonly written as BRAF V600E — this refers to a specific change in the BRAF gene found in a large proportion of thyroid cancers. BRAF testing is now a routine part of the molecular workup for thyroid cancer, and the result can carry very different implications depending on the type of thyroid cancer you have. In some thyroid cancers, a BRAF mutation is a prognostic marker that indicates how the cancer is likely to behave. In others — particularly anaplastic thyroid carcinoma — it identifies you as a candidate for a specific targeted drug combination that can make a meaningful difference to survival. This article explains what BRAF testing looks for and what the result means for your particular cancer.

What the test looks for

The BRAF gene provides the instructions for making a protein — also called BRAF — that sits within a signalling chain inside cells known as the MAPK pathway. This pathway acts like a relay system: it carries signals from the cell surface inward, telling the cell when to grow and divide. In a healthy cell, BRAF switches on when needed and switches off again when the signal is done.

The BRAF V600E mutation — the name refers to a specific change at position 600 in the BRAF protein, where the amino acid valine is replaced by glutamic acid — disrupts this off switch. The result is a permanently activated BRAF protein that continuously drives cell growth and division, regardless of whether external signals are present. This permanently active signalling is one of the core mechanisms by which cancers develop and grow.

BRAF V600E is by far the most common BRAF mutation found in thyroid cancer, accounting for the large majority of BRAF-positive cases. Other BRAF mutations exist but are rare in thyroid tumours. When a pathology report refers to a BRAF mutation in thyroid cancer without further specification, it almost always means V600E.

The BRAF gene is also relevant in thyroid cancer because of its connection to specific thyroid cancer subtypes and its role as a target for drugs that directly block the abnormal BRAF protein.

Why is the test done

BRAF testing in thyroid cancer serves three overlapping purposes, and which one is most relevant to you depends on the type of thyroid cancer you have been diagnosed with.

The first purpose is diagnostic support. BRAF V600E is found in approximately 40–60% of all papillary thyroid carcinomas — the most common type of thyroid cancer — and is strongly associated with the classic and tall cell subtypes of papillary carcinoma. Its presence, combined with the characteristic appearance of the tumour under the microscope, helps confirm the diagnosis. In cases where the findings are ambiguous — for example, on a fine needle aspiration biopsy where the cells look suspicious but not definitively malignant — a positive BRAF V600E result substantially increases the probability that the nodule is cancerous. Some molecular testing panels for thyroid nodules include BRAF specifically for this reason.

The second purpose is prognostic assessment. Within papillary thyroid carcinoma, the presence of a BRAF V600E mutation is associated with features of more aggressive behaviour — including extrathyroidal extension (spread beyond the thyroid capsule), lymph node metastases, and higher rates of recurrence — and with a reduced ability of the tumour to take up radioactive iodine, which is one of the main treatments for thyroid cancer that has spread. This prognostic information can influence decisions about the extent of surgery, the use of radioactive iodine therapy, and the intensity of follow-up.

The third purpose — and the most urgent — is treatment selection. In anaplastic thyroid carcinoma, which is one of the most aggressive human cancers, approximately 40–50% of tumours carry a BRAF V600E mutation. For patients with BRAF V600E-positive anaplastic thyroid carcinoma, a targeted drug combination — dabrafenib plus trametinib — is approved and has produced response rates and survival outcomes that represent a significant advance over previous treatment. In this setting, BRAF testing is not optional; it is an urgent, treatment-defining test that should be performed at the time of diagnosis. Similarly, in patients with poorly differentiated thyroid carcinoma or differentiated thyroid cancer that has stopped responding to radioactive iodine, BRAF V600E status informs eligibility for targeted therapy.

Who should be tested

BRAF testing is appropriate across a range of thyroid cancer diagnoses and clinical scenarios:

Patients with papillary thyroid carcinoma. BRAF V600E testing is increasingly performed as standard practice in papillary thyroid carcinoma, particularly in cases with aggressive histological subtypes (tall cell, hobnail, columnar cell), advanced stage at presentation, or features suggesting a higher risk of recurrence. Many centres perform reflex molecular testing on all papillary thyroid carcinoma resections.
Patients with anaplastic thyroid carcinoma. BRAF V600E testing should be performed urgently at diagnosis. Given the rapid progression of this cancer, results are needed quickly to determine whether dabrafenib plus trametinib can be initiated as part of the treatment plan.
Patients with poorly differentiated thyroid carcinoma. BRAF V600E testing is appropriate for treatment planning, particularly in patients with advanced or metastatic disease who may be candidates for targeted therapy or clinical trials.
Patients with thyroid nodules with indeterminate fine-needle aspiration. When a biopsy of a thyroid nodule produces an indeterminate result — meaning it is unclear whether the cells are benign or malignant — molecular testing panels that include BRAF V600E can help guide the decision about whether surgery is needed.
Patients with radioiodine-refractory differentiated thyroid cancer. When differentiated thyroid cancer (papillary or follicular) has spread and stopped taking up radioactive iodine — making that treatment ineffective — BRAF status is part of the molecular profiling used to identify alternative systemic therapy options.

How the test is performed

BRAF V600E testing in thyroid cancer can be performed using several methods, and the approach depends on the clinical context and the tissue available.

The most common method is next-generation sequencing (NGS) — a technology that reads the genetic code of the tumour across many genes simultaneously. NGS is increasingly the default approach in thyroid cancer because it identifies BRAF mutations alongside other clinically relevant alterations (including RAS mutations, RET fusions, and TERT promoter mutations) in a single test. This is particularly valuable because some treatment and prognostic decisions in thyroid cancer depend on the full molecular picture rather than BRAF status alone.

For faster results — which matters most in anaplastic thyroid carcinoma, where treatment decisions are urgent — targeted PCR-based testing or immunohistochemistry may be used. A specific antibody that recognises only the V600E mutant form of the BRAF protein is available for immunohistochemical staining, enabling the laboratory to screen for the mutation on a tissue slide rapidly. A positive immunohistochemistry result is usually confirmed with sequencing.

All of these tests are performed on tumour tissue — the specimen removed during surgery or obtained during a biopsy. In the case of anaplastic thyroid carcinoma, where time is critical, a core needle biopsy may be performed specifically to obtain tissue for urgent molecular testing before or alongside surgical planning.

How results are reported

BRAF results in thyroid cancer are typically reported in one of the following ways:

BRAF V600E mutation detected. The specific V600E mutation has been identified in the tumour. This is a positive result. The report will usually specify the method used (NGS, PCR, or immunohistochemistry) and may include the variant allele frequency — a measure of the proportion of tumour cells carrying the mutation.
No BRAF mutation detected. No BRAF V600E mutation (or other BRAF mutation) was found in the tumour. This is a negative result. In the context of a broader NGS panel, the report may also confirm the absence of other BRAF alterations beyond V600E.
BRAF V600E positive by immunohistochemistry. When immunohistochemistry is used as a screening test, the result is reported as positive or negative based on the staining pattern. A positive IHC result is highly specific for V600E and is generally treated as equivalent to a mutation-detected result, though confirmation by sequencing may be performed.

When NGS is used, the report may also include results for other relevant genes — such as RAS, RET, TERT, and TP53 — alongside the BRAF result. The full panel result, rather than the BRAF result in isolation, is what your oncologist or endocrinologist will use to guide management.

What the result means

What a BRAF V600E result means for you depends significantly on your thyroid cancer diagnosis. The sections below address each major clinical context separately.

Papillary thyroid carcinoma

In papillary thyroid carcinoma, BRAF V600E is the most common molecular alteration found, present in roughly 40–60% of cases. Its presence is associated with several features of more aggressive behaviour: tumours with BRAF V600E mutations are more likely to show extrathyroidal extension, lymph node metastases at diagnosis, and multifocal disease within the thyroid. They are also more likely to lose the ability to take up radioactive iodine. This capacity depends on the tumour retaining sufficient resemblance to normal thyroid tissue to express the sodium-iodine symporter protein.

For most patients with localised papillary thyroid carcinoma, a BRAF V600E result influences risk stratification and follow-up intensity rather than triggering immediate targeted drug therapy. The American Thyroid Association’s risk stratification system and similar guidelines incorporate BRAF V600E status — particularly when combined with other high-risk features — in classifying patients as intermediate or high risk for recurrence. This may influence recommendations around the extent of surgery (lobectomy versus total thyroidectomy), the use and dose of radioactive iodine after surgery, and the frequency and type of surveillance imaging.

BRAF V600E is particularly strongly associated with the tall cell, hobnail, and columnar cell subtypes of papillary thyroid carcinoma — all of which carry a worse prognosis than the classic subtype. If your pathology report identifies one of these subtypes, a BRAF V600E result adds to the picture of a higher-risk cancer.

For patients with papillary thyroid carcinoma that has spread to distant sites and become refractory to radioactive iodine therapy, BRAF V600E status becomes directly relevant to systemic treatment. Targeted therapies, including the combination of dabrafenib and trametinib, are approved or under evaluation in this setting.

Anaplastic thyroid carcinoma

In anaplastic thyroid carcinoma, BRAF V600E is found in approximately 40–50% of cases, typically in tumours that arose from a pre-existing papillary thyroid carcinoma. Here, the result is not simply prognostic: it is directly treatment-defining, and it matters urgently.

The combination of dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor — a drug that blocks a protein directly downstream of BRAF in the same signalling pathway) was approved by the FDA in 2018 for BRAF V600E-mutated anaplastic thyroid carcinoma. This approval was based on data showing an overall response rate of approximately 56% in patients with BRAF V600E-positive anaplastic thyroid carcinoma — a remarkable result for a cancer that had previously had almost no effective systemic treatment options. Responses included both partial and complete responses, with some patients experiencing durable disease control.

This is a cancer in which the median survival without effective treatment is measured in months, and in which a targeted therapy achieving a response rate exceeding 50% represents a genuine clinical transformation for eligible patients. Identifying BRAF V600E status at diagnosis — and initiating dabrafenib plus trametinib rapidly when the mutation is present — is now a central part of the management of anaplastic thyroid carcinoma.

Dabrafenib plus trametinib is often given in combination with surgery, radiation, and other systemic therapies as part of a multimodal treatment plan. Your medical team will advise on the sequence and combination appropriate to your situation.

Poorly differentiated thyroid carcinoma

Poorly differentiated thyroid carcinoma occupies a clinical and biological position between well-differentiated papillary/follicular carcinoma and anaplastic thyroid carcinoma. BRAF V600E is found in a subset of these tumours, and when present alongside other high-risk molecular features (particularly TERT promoter mutations), it is associated with a more aggressive course.

In patients with metastatic or unresectable poorly differentiated thyroid carcinoma that has become refractory to radioactive iodine, BRAF V600E status is part of the molecular profiling used to determine systemic therapy options — including BRAF/MEK inhibitor combinations and participation in clinical trials.

BRAF-negative result

A negative BRAF result means no BRAF V600E mutation was found. In papillary thyroid carcinoma, this is consistent with roughly 40–60% of cases — BRAF V600E-negative papillary carcinomas are common and are not, on that basis alone, lower-risk tumours; other molecular alterations (RET fusions, RAS mutations, TERT promoter mutations) may still be present and clinically relevant.

In anaplastic thyroid carcinoma, a BRAF-negative result means the dabrafenib plus trametinib combination is not indicated, and treatment will focus on other systemic options, including immunotherapy, chemotherapy, and clinical trials. Your oncologist will discuss the alternatives appropriate to your situation.

What happens next

For patients with papillary thyroid carcinoma, a BRAF V600E result will be incorporated into your overall risk assessment alongside tumour size, stage, subtype, and other pathological features. Your endocrinologist, thyroid surgeon, and nuclear medicine specialist will use this information to advise on the need for total thyroidectomy versus lobectomy (if surgery has not yet been performed), the use and dosing of radioactive iodine, thyroid hormone suppression therapy, and the schedule and type of follow-up imaging and blood tests. For most patients with localised papillary carcinoma, a BRAF V600E result does not trigger targeted drug therapy — it refines risk and follow-up planning.

For patients with anaplastic thyroid carcinoma, if your BRAF result is positive, your medical team will discuss initiating dabrafenib plus trametinib as part of your treatment plan as quickly as possible. Given the speed at which anaplastic thyroid carcinoma progresses, time matters, and the result should be available urgently. Your team should include a medical oncologist experienced in thyroid cancer, alongside a thyroid surgeon and a radiation oncologist.

For patients with radioiodine-refractory differentiated or poorly differentiated thyroid cancer, the BRAF result will be considered alongside the full molecular profile when deciding between available systemic therapy options, which may include BRAF/MEK inhibitor combinations, multi-kinase inhibitors (such as sorafenib, lenvatinib, or cabozantinib), or clinical trials.

If molecular testing has not yet been performed on your thyroid cancer — particularly if you have anaplastic or poorly differentiated thyroid carcinoma, or differentiated thyroid cancer that has become refractory to radioactive iodine — it is worth asking your oncologist or endocrinologist whether testing is available and appropriate.

Questions to ask your doctor

Has BRAF testing been performed on my tumour, and if so, what were the results?
Was BRAF the only gene tested, or was a broader molecular panel performed? Are there other results I should know about?
How does the BRAF result change my risk classification or treatment plan compared to what it would be without this finding?
If I have anaplastic thyroid carcinoma and my BRAF result is positive, when can treatment with dabrafenib and trametinib begin, and what should I expect?
If my BRAF result is negative, what other molecular alterations are present, and do any of them have treatment implications?
Does my BRAF result affect decisions about radioactive iodine therapy or the extent of surgery?
Are there clinical trials I should be aware of based on my BRAF result or overall molecular profile?