Gene expression (GE) profiling has emerged as a promising means of uncovering the biology of multiple myeloma and of developing new prognostic models.(1-3) CD138 (syndecan 1) is a highly specific marker of plasma cells and a central mediator of growth and progression in myeloma.(4) Hence, CD138+ separation has proven useful as a sample handling step in myeloma GE studies.(5-7) However, it is unclear how the sample handling affects the myeloma cells. We hypothesized that CD138+ separation would induce changes in genes related to myeloma pathogenesis. To address this question, we treated human myeloma cell lines (HMCL) as if they were myeloma bone marrow samples and compared the GE between separated and unseparated cells. This article is protected by copyright. All rights reserved.