Five cases were treated by adding daily low-dose thalidomide (50 mg) to bortezomib and dexamethasone therapy for refractory multiple myeloma. This therapy was effective in four cases, with an improvement of bone pain and regression of M-protein. One case was treated with cyclophosphamide, thalidomide, and dexamethasone, adding bortezomib after starting the three-drug combination therapy. This patient has remained in a stable disease state since the beginning of this therapy. Regarding the other four cases, a partial response and a prolonged survival for approximately one year were noted. Peripheral neuropathy did not increase after thalidomide addition. Adding low-dose thalidomide may safely improve the responses for multiple myeloma refractory to bortezomib and dexamethasone.