In some patients with multiple myeloma, extramedullary masses may be present at diagnosis or may develop during treatment. Recently, multiple myeloma has been treated using newer therapeutic regimens based on thalidomide and bortezomib. Using these drugs, positive responses to treatment, not found with conventional antineoplastic agents, have been reported along with an improvement in patient outcome. In the present study, we report on three patients with extramedullary masses associated with multiple myeloma. Although all three patients were treated with bortezomib, it was ineffective against the extramedullary masses and the clinical course of the disease differed between the three patients. We propose that the effects of bortezomib on extramedullary masses may differ from case to case and may not be evident in cases of severe disease. Also, the effects of bortezomib may not be evident in the case of myeloma cells that have left the bone marrow microenvironment, similar to thalidomide. In addition, resistance to bortezomib may manifest as extramedullary masses. (160 words in the body of abstract).