CD20 has been reinvestigated in 66 patients with multiple myeloma (MM). Twelve of the patients (18%) expressed CD20, including 5 of 50 patients at diagnosis presenting 100% CD20+ cells. Seven (58%) of 12 CD20+ patients with MM had a small mature plasma cell morphology as opposed to 4 (7%) of 54 with CD20- MM (P =.0001). Of note, 10 (83%) of 12 patients with CD20+ MM had t(11;14) as opposed to 5 of 54 (9%) CD20- patients (P <.001). All the patients with 100% CD20+ cells presented with t(11;14) and 4 of 5 with a small mature plasma cell morphology. Thus, 66% of the patients with t(11;14) expressed CD20, whereas only 4% of the 51 patients lacking such translocation expressed CD20 (P <.0001). In conclusion, CD20 expression is associated with small mature plasma cell morphology and with t(11;14) in patients with MM.