Using Affymetrix microarrays, we identified the expression of the CD200 gene in multiple myeloma cells (MMCs) of 112 patients with newly diagnosed multiple myeloma (MM). The CD200 gene was either absent or present (Affymetrix call) in 22% and 78% of MMCs, respectively. The CD200 gene is not expressed in cells of the patients' bone marrow (BM). CD200 is a membrane glycoprotein that imparts an immunoregulatory signal through CD200R, leading to the suppression of T-cell–mediated immune responses. Patients with CD200_absent MMCs have an increased event-free survival (EFS; 24 months) compared with patients with CD200_present MMCs (14 months), after high-dose therapy and stem cell transplantation. In a Cox proportional-hazard model, the absence or presence of CD200 expression in MMCs is predictive for EFS for patients independently of ISS stage or β2M serum levels. Thus, CD200 is an independent prognosis factor for patients with MM that could represent a new therapeutic target in MM.