Expression of CD19 and lack of miR-223 distinguish extramedullary plasmacytoma from multiple myeloma. AIMS: Extramedullary plasmacytoma (EMP) and multiple myeloma (MM) are both plasma cell (PC) tumours that are usually distinguished by clinical manifestations, but not by histopathological examination alone. However, EMP may express B-cell markers, such as CD79a and CD20, and MM may express germinal centre B-cell (GCBC)-associated microRNAs, such as miR-93 and miR-181b . Down-regulation of miR-30a or up-regulation of miR-223 is associated with the transition from GCBCs into PCs or memory B-cells, respectively. We studied B-cell markers and microRNAs to establish criteria that could distinguish EMP from MM. METHODS AND RESULTS: Immunostains for the B-cell markers CD19, CD20, CD79a and PAX5 were performed. Expression levels of microRNAs 30a, 93, 181b and 223 were measured by real-time reverse transcription polymerase chain reactions. 73% of EMPs expressed CD19 whereas MM cases were negative. EMP and MM had similar levels of miR-30a, miR-93, and miR-181b, but EMP lacked expression of miR-223 . CONCLUSIONS: The presence of CD19 and lack of miR-223 suggested aberrant B-cell differentiation in EMP. Although the underlying mechanism for this differential expression was unclear, a CD19 (+)/miR-223 (-) phenotype could be used to distinguish EMP from the CD19 (-)/miR-223 (+) phenotype of MM.