Two patients, 51- and 45-year-old men with stage III immunoglobulin G multiple myeloma, achieved partial and complete remissions, respectively, after conventional chemotherapy. They both received high-dose melphalan (200 mg/m2) with autologous stem cell transplantation (ASCT). Eighty-four and 78 days after ASCT, the patients underwent unrelated cord blood transplantation (CBT) following treatment with total-body irradiation (2 Gy), fludarabine (90 mg/m2), and melphalan (140 mg/m2). Neutrophil engraftment was attained on day +27 in patient 1 and day +15 in patient 2. Full donor chimerism of the marrow cells was confirmed. Regimen-related toxicity in both patients remained within grade I. Grades I and II acute graft-versus-host disease (GVHD) occurred in patients I and 2, respectively, but improved without steroid therapy. Both patients developed limited chronic GVHD of the skin but needed no treatment. The serum paraprotein level in patient 1 decreased further after ASCT and CBT but remained at minimally detectable levels. The serum and urine paraprotein levels in patient 2 remained below detectable limits. These results suggested that CBT with a reduced-intensity conditioning regimen after high-dose chemotherapy with ASCT is a new promising approach for the treatment of multiple myeloma.