Multiple myeloma (MM) is a malignant disease resulting from an uncontrolled proliferation of a neoplastic plasma cell clone in the bone marrow, which might also be induced by the loss of control on apoptosis. Fas ligand (Fas-L), a member of the tumor necrosis factor family, induces apoptosis mediated via its transmembrane death receptor Fas (Apo-1/CD95) antigen. In the present study, immunostaining was performed on the initial diagnostic bone marrow biopsies of 36 MM patients (1 stage I, 5 stage II, 30 stage III), to evaluate the distribution of Fas receptor and Fas-L on malignant plasma cells. Both Fas and Fas-L were positive in 13 cases and negative in 3, whereas 10 cases were Fas-negative, Fas-L-positive and 10 were Fas-positive, Fas-L-negative. Although no association was found between the expression of Fas receptor or Fas-L and overall survival, Fas-L positivity was significantly associated with a shorter event-free survival (p = 0.0335). In this study, it has been shown that the expression of Fas-L, in malignant plasma cells of myeloma patients significantly shortens the event-free survival, indicating that the defect in apoptosis might be associated with disease progression in MM.