Background: The aims of this study were to establish the clinical value of multi-parametric flow cytomentry (MFC) in multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Methods: We analyzed bone marrow aspirates from 112MMand 17 MGUS patients by MFC, using 3 combinations of 9 color labeling: a, CD38 / CD138 / CD45 / CD56 / CD19 / CD27 / CD117 / CD20 / CD33; b, CD38 / CD138 / CD45 / cytoplasmic Kappa / cytoplasmic Lambda; and c, CD38 / CD138. MFC data were classified based on clinical features and prognosis factors. Results: Myeloma’ s patients compared to MGUS group had plasma cells (PCs) with abnormal immunophenotypic patterns, including high CD56 and CD20 expression and weak or negative CD45, CD19, and CD27 expression without significant median differences in expression of CD33 and CD117. Multiple myeloma patient with low expression of CD19, CD27 or CD45, overexpression of CD56 or with a high proportion of PCs at diagnosis demonstrated shorter overall survival times. Moreover, MMpatients with combined abnormal expressions of 4 or 5 antigens demonstrated shorter survival times (P = 0. 001). These high-risk MFC patients were associated with poor clinical outcomes, including ISS stage III and DS stage III, low hemoglobin levels, and elevated serum beta2-microglobilin (P = 0. 01, P = 0. 006, P = 0. 01 and P = 0. 008, respectively). Conclusions: The present study highlights the benefits of assessing abnormal antigen expression for clinical uses. These measures could facilitate proper diagnosis of disorders and improve risk stratification for a targeted early treatment regimen.