OBJECTIVE: Multiple myeloma is a plasma cell neoplasm characterized by the accumulation of malignant plasma cells within the bone marrow. This disease remains incurable despite major treatment improvements. However, gene expression profiling of multiple myeloma cells (MMC) may lead to identification of new therapeutic targets. MATERIALS AND METHODS: Using Affymetrix microarrays, we identified the overexpression of the MYEOV gene in MMC of 171 patients with newly diagnosed multiple myeloma compared to normal plasma cells. RESULTS: The MYEOV gene was present (Affymetrix call) in 79% of MMC and in 15% of normal plasma cells. MYEOV gene is not expressed in cells of the patients' bone marrow environment. The downregulation of MYEOV gene reduced the growth of a MYEOV(present) myeloma cell line, unlike a MYEOV(absent) one. Patients with MYEOV(absent) MMC have an increased event-free survival compared to patients with MYEOV(present) MMC, after high-dose therapy and stem cell transplantation and a trend for increased overall survival. In a Cox proportional hazard model, MYEOV expression in MMC is predictive for event-free survival for patients independently of International Staging System stage, t(4;14) translocation, albumin, or B2M serum levels. A knockout of MYEOV significantly reduced the growth of MMC. CONCLUSIONS: Thus, MYEOV expression is a prognostic factor for patients with multiple myeloma, in part through a role of MYEOV in the control of MMC proliferation.