Multiple myeloma (MM) is a neoplastic disease characterized by proliferation and prolonged survival of clonal plasma cells, most frequently occurring in the bone marrow, but also in other tissues. Dendritic cells (DCs) are a heterogeneous population of leukocytes defined as professional antigen presenting cells playing a key role in anticancer immunity. The purpose of this study was to evaluate subpopulations of myeloid and lymphoid DCs in the peripheral blood (PB) and bone marrow (BM) of patients with MM in the different clinical stages of MM and in correlation with known prognostic factors. The study involved 50 patients diagnosed with MM before the initiation of anticancer therapy and 25 individuals belonging to the control group. The mean percentage of myeloid and lymphoid DCs was determined using flow cytometry. In the present study, we demonstrated a significant reduction in the percentages of both myeloid and lymphoid DCs in MM patients, more pronounced in those with the worse prognosis as determined by the high levels of β2 microglobulin. Accordingly, a marked decrease in the proportions of both myeloid and lymphoid DCs in the BM of patients with advanced clinical stage (III) compared to earlier stages (I+II) was also found. Our results suggest that the degree of DC subpopulations deficit could be related to the MM progression, which in consequence may contribute to the MM-related impairment of the immune responses.