Cluster of differentiation 21 (CD21) is a glycoprotein on the surface of B-cells that is bound by Epstein-Barr virus (EBV) during infection of these cells. CD21 staining is useful for recognizing follicular dendritic cell matrices in normal tonsillar and lymph tissue, and can also stain dendritic cell sarcomas. CD21 is also useful for distinguishing marginal zone lymphoma with follicular involvement from follicular lymphoma with marginal zone differentiation. When used in concert with other B- and T-cell markers, CD21 is valuable for the differentiation between nodular lymphocyte-predominant Hodgkin lymphoma, T-cell/histiocyte-rich B-cell lymphoma, and lymphocyte-rich classic Hodgkin lymphoma. CD21 staining is useful for recognizing abnormal follicular dendritic cell patterns in angioimmunoblastic T-cell lymphoma and follicular T-cell lymphoma.