Primary effusion lymphoma (PEL) is a peculiar B‐cell lymphoma characterized by infection by human herpesvirus type‐8/Kaposi sarcoma‐associated herpesvirus (HHV‐8/KSHV) and by preferential growth in the serous body cavities. Histogenetic studies have suggested that PEL originates from B cells at a late stage of differentiation. In this study, we have investigated PEL for the expression status of MUM1/IRF4 (multiple myeloma 1/interferon regulatory factor 4) protein, which is involved in physiological B‐cell maturation and represents a histogenetic marker of late B‐cell differentiation. Using multiple detection assays, all cases of PEL (n = 22) were found to express MUM1/IRF4 molecules. MUM1/IRF4 expression was a selective feature of PEL among lymphomas involving the serous body cavities as secondary lymphomatous effusions generally failed to express the protein. In reactive lymphoid tissues, MUM1/IRF4 expression clustered with advanced stages of B‐cell differentiation. Comparison of MUM1/IRF4 expression with that of other histogenetic markers defined two phenotypic variants of PEL, i.e. MUM1/IRF4⁺, CD138/syndecan‐1⁺, B‐cell antigen⁻ (20 out of 22 cases) and MUM1/IRF4⁺, CD138/syndecan‐1⁻, B‐cell antigen⁺ (2 out of 22 cases), suggesting a certain degree of heterogeneity in the disease histogenesis. The implications of these data are threefold. First, MUM1/IRF4 expression corroborates the notion that PEL originates from post‐germinal centre, preterminally differentiated B‐cells. Second, MUM1/IRF4 may help in the differential diagnosis of PEL among other lymphomas involving the serous body cavities. Finally, MUM1/IRF4 may interact with HHV‐8/KSHV‐encoded interferon regulatory factors (IRFs) and thus contribute to PEL escape from interferon‐mediated control of viral infection.