Two multiple myeloma patients relapsed after autologous stem cell transplantation (ASCT). Conventional chemotherapy, including thalidomide, showed very little effect, but both patients responded well to a standard dose of bortezomib. One patient was treated with two additional cycles of bortezomib, but his clinical course suddenly deteriorated. Unrelated cord blood transplantation (CBT) with reduced-intensity conditioning regimen (RIC) was performed in refractory disease. After CBT, the clinical course was aggravated by tumor lysis syndrome and other conditions, thus resulting in patient death on day 34. Thereafter, we administered CBT with RIC on the second patient after just one course of bortezomib therapy since she was in partial remission. The second patient developed acute and chronic GVHD, and both responded to the steroid therapy. She has been in complete remission for more than 48 months after CBT. These results suggested that the timing of CBT with RIC may be very important, and cytoreduction with not only ASCT but also bortezomib could give a promising chance for a successful CBT.