Aims: A number of clinicopathological features have been attributed to the CD20 positive subset of plasma cell myeloma (PCM). CD20 is an appealing therapeutic target given the success with monoclonal antibody regimens in a spectrum of B cell lymphomas. To date, a small number of reports have described CD20+ PCM as a unique subset, and these are not conclusive, especially taking into consideration reporting bias. This study aims to further identify the clinicopathological features of CD20 + PCM. Methods: A retrospective analysis of all newly diagnosed PCM between 2003 and 2010 was undertaken. Trephine material was retrieved and reviewed for CD20, and for positive cases an extended immunohistochemical (IHC) panel including cyclin D1 was subsequently performed. Results: The review of our 40 cases and those described in the literature demonstrated that these are heterogeneous with regard to clinical features, morphology, biochemical features, immunophenotype, and cytogenetics. Conclusion: Based on our study and review of the literature, CD20 + PCM cases represent a heterogeneous disease and not a unique clinicopathological entity. ? 2012 Royal College of Pathologists of Australasia.