Myeloma is a neoplasm of post-germinal center B-cell derivation with plasmacytic differentiation. The tumor cells show strong expression of CD38, CD138 (syndecan-1) (shown here), CD79a, VS38c, and MUM-1/IRF4. There is strong cytoplasmic expression of light chains with kappa or lambda restriction. Almost 70% of multiple myelomas express CD56; however, almost 80% of plasma cell leukemias are CD56 negative. In typical cases, there is no expression of pan B-cell antigens such as CD19, CD20, Pax-5, nor CD45. Exceptions do occur. A small subset of myelomas expresses CD20. Some cases with t(11;14)(q13;q32) translocation resemble mantle cell lymphoma and express cyclinD1, CD19, CD20, and Pax-5 along with plasmacytic markers such as CD138 and MUM-1. In such cases, the diagnosis of myeloma rests on clinical presentation. The image shows replacement of entire marrow by CD138 positive plasma cells. IHC stain. 40X. Courtesy of: Jian-Hua Qiao, MD, FCAP, Los Angeles, CA, USA.