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CD138-negative plasma cell myeloma: a diagnostic challenge and a unique entity. Plasma cell neoplasms may exhibit variations in morphology and immunophenotype, which can mimic mature B-cell lymphoproliferative disorders and pose diagnostic challenges. This case illustrates a rare entity of plasma cell myeloma, where the entire plasma cell population exhibited lymphoid morphology, negativity for CD138, positivity for CD20 and cyclin D1, and positive fluorescence in situ hybridisation for t(11;14) and del(17 p), mimicking a mature B-cell lymphoproliferative disorder, in particular mantle cell lymphoma. In this case, a careful analysis of flow cytometry gating strategies and use of other ancillary tests were keys for correct diagnosis. In addition to the diagnostic implications due to its rarity, CD138-negative plasma cell myeloma may represent a unique entity, which is associated with 'stem cell'-like clonogenic properties, more aggressive clinical behaviour and resistance to chemotherapy.