The interaction between multiple myeloma (MM) cells and the bone marrow stroma constitutes the basis of myeloma pathogenesis and has led the way for the corresponding therapeutic strategies. The aim of this study is to evaluate tumor-associated macrophages (TAMs) which is an important element of bone marrow stroma and its prognostic relevance in newly diagnosed MM patients. We also wanted to determine the association between TAMs and microvessel density (MVD). Sixty-eight patients, who were diagnosed with MM at the Department of Hematology, Gazi University Hospital, between January 2000 and January 2011, were reviewed retrospectively. Tumor-associated macrophages were evaluated by staining with anti-CD68 and anti-CD163 monoclonal antibodies, and MVD was evaluated by factor VIII staining. Median age was 60 (range, 40-84) years with 36 males and 32 females. The number of both CD 68+ and CD 163+ cells had a negative impact on OS at 6 years (p = 0.013 vs. 0.036; p = 0.015 vs. 0.039) in univariate and multivariate analysis in which age, sex, ISS, the induction treatment, and response to induction treatment are included as variables. High-grade MVD was found to be associated with increased CD163+ cell count. In conclusion, TAMs seems to be a promising prognostic histopathological marker in newly diagnosed MM patients.