We reviewed bone marrow studies from 351 multiple myeloma (MM) cases, selecting 12 cases (3.4%) with predominantly small lymphocyte-like morphologic features resembling B-cell lymphoma, and correlated their genetic and clinical features. All exhibited a diffuse interstitial pattern of marrow involvement. Small lymphocyte-like plasma cells were all CD45- with bright CD38 and CD138 expression and CD20 expression in 5 cases. No case had an increase in bone marrow B lymphocytes by flow cytometry. Of 12 cases, 9 were classified as the CD-2 molecular class by gene expression profiling (GEP). The 29 CD-2 class cases with (n = 9) and without (n = 20) small lymphocyte-like features could not be discerned from one another using global GEP. Event-free, but not overall, survival was significantly better in cases with small lymphocyte-like features among those sharing the CD-2 subtype. Small lymphocyte-like MM is a rare, morphologically challenging variant distinguished from B-cell lymphoma by lack of CD45 and presence of CD138 and the clinical presentation of MM. Most cases share a common GEP signature dominated by hyperexpression of cyclin D1 or cyclin D3 genes, with increased expression of the B-cell genes CD20 and VPREB3.