CD20: Definition

CD20 is a protein found on the surface of B cells — a type of white blood cell that helps the body fight infections by producing antibodies (proteins the immune system uses to recognize and attack germs). CD20 appears on B cells as they mature in the bone marrow and remains on the cell’s surface throughout most of the cell’s life, but it is lost when B cells become plasma cells, the antibody-producing cells found in tissue. In pathology, CD20 is one of the most reliable markers for identifying B cells, diagnosing B-cell lymphomas, and guiding treatment. CD20 is also the target of one of the most widely used cancer drugs in the world — rituximab — and several other modern treatments for B-cell cancers.

Why do pathologists test for CD20?

CD20 is tested for two main reasons:

To identify B cells in a tissue sample. Because CD20 is reliably present on most B cells, it is one of the most useful markers for confirming a tumor’s B-cell origin. This is essential for diagnosing and classifying B-cell lymphomas — cancers of the immune system that arise from B cells.
To identify candidates for CD20-targeted therapy. CD20 is the molecular target of several powerful cancer treatments, most notably rituximab (Rituxan). Confirming that a tumor’s cells carry CD20 is a prerequisite for using these therapies — they only work on CD20-positive cells.

How is CD20 tested?

CD20 can be detected using two laboratory techniques, often used together:

Immunohistochemistry (IHC) — performed on a thin slice of tissue placed on a glass slide. An antibody (a protein designed to attach specifically to CD20) is applied to the tissue, producing a color change visible under the microscope wherever CD20 is present.
Flow cytometry — a laboratory test that uses a special machine to examine individual cells one by one in a sample of blood, bone marrow, or lymph node tissue. The machine can rapidly identify and count cells carrying CD20 and other markers, providing detailed information about the cell types present.

How results are reported

CD20 results are reported as positive or negative, often with additional detail about how strongly the cells stain:

Positive (reactive) — CD20 protein is detected on the cells. In a suspected B-cell lymphoma, a positive result confirms that the cancer cells are B cells. This finding is also essential for treatment decisions, since CD20-positive cancers may be candidates for rituximab and related therapies. The pathologist may describe the staining as strong (bright), weak (dim), or partial — patterns that can help classify specific lymphoma subtypes.
Negative (non-reactive) — CD20 protein is not detected. A negative result helps rule out a B-cell origin or, in the right context, supports a diagnosis of a plasma cell cancer (such as multiple myeloma), which normally loses CD20. A previously CD20-positive lymphoma that becomes CD20 negative after rituximab treatment may indicate that the cancer has changed and may no longer respond to that therapy.

How does CD20 fit with other B cell markers?

CD20 is typically tested alongside other B-cell markers, each of which provides slightly different information:

CD19 — like CD20, CD19 appears early in B-cell development. Unlike CD20, however, CD19 remains present on plasma cells, making it useful for identifying plasma cell tumors that lack CD20.
PAX5 — a transcription factor (a type of protein that controls gene activity) found in the nucleus of B cells; useful for confirming B-cell identity, especially when surface markers are unclear.
CD79a and CD79b — proteins that work together with CD20 in B-cell signaling and are present on most B cells.

Using these markers in combination allows the pathologist to reliably confirm B-cell origin and classify the specific type of lymphoma.

Which cancers are typically CD20 positive?

Most cancers that arise from B cells are CD20 positive. The most common include:

Chronic lymphocytic leukemia (CLL) — a slow-growing cancer of mature B cells, usually found in adults. CLL characteristically expresses CD20 weakly (described as “dim”).
Small lymphocytic lymphoma (SLL) — closely related to CLL, but the cancer cells are mainly found in lymph nodes rather than circulating in the blood.
Follicular lymphoma — a slow-growing B-cell lymphoma that arises from cells in the germinal centers of lymph nodes (specialized regions where B cells normally develop).
Diffuse large B-cell lymphoma (DLBCL) — the most common aggressive B-cell lymphoma; CD20 testing is essential because rituximab combined with chemotherapy is the standard first-line treatment.
Mantle cell lymphoma — an aggressive B-cell lymphoma that often spreads widely at the time of diagnosis.
Marginal zone lymphoma — a slow-growing B-cell lymphoma that can develop in lymph nodes, the spleen, or in tissues outside the lymphatic system, such as the stomach.

What does CD20 mean for treatment?

CD20 is one of the most important treatment targets in cancer medicine. Several treatments specifically target CD20-positive cells:

Rituximab (Rituxan) — the first targeted cancer therapy of its kind. Rituximab is an antibody that attaches to CD20 on B cells, marking them for destruction by the immune system. Combined with chemotherapy, rituximab has dramatically improved outcomes in DLBCL, follicular lymphoma, and many other B-cell lymphomas. It is also used in non-cancerous autoimmune diseases such as rheumatoid arthritis.
Newer anti-CD20 antibodies — drugs such as obinutuzumab and ofatumumab are more recent CD20-targeted antibodies that are designed to be more potent than rituximab and may be used when rituximab is not effective.
Bispecific antibodies — drugs such as mosunetuzumab, glofitamab, and epcoritamab are laboratory-made proteins designed to attach simultaneously to CD20 (on the cancer cell) and to a marker on healthy T cells (a type of immune cell), bringing the two together so the immune system can destroy the cancer cell. These are used for relapsed or treatment-resistant B-cell lymphomas.

Confirmation of CD20 expression on the cancer cells is required before any of these treatments can be used. If CD20 is later lost — sometimes a way that cancers escape these therapies — additional testing and a change in treatment may be needed.

Questions to ask your doctor

Was CD20 tested in my tumor or blood, and what was the result?
Does my CD20 result confirm that my cancer is a B-cell type?
Am I a candidate for rituximab or another CD20-targeted treatment?