A 69-year-old Japanese man was diagnosed as having primary plasma cell leukemia. His malignant plasma cells had a chromosomal translocation t(11;14)(q13;q32) that created overexpression of cyclin D1. Two courses of VAD (vincristine, doxorubicin, dexamethasone) therapy failed to achieve complete remission. Three subsequent courses of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) therapy successfully induced remission with negative FISH test for t(11;14)(q13;q32). Thereafter, the patient received high-dose melphalan (125 mg/m(2)) followed by autologous peripheral blood stem cell transplantation. Cyclin D1 that was present prior to the high-dose chemotherapy, was no longer detected by qualitative PCR analysis. Despite complete cytogenetic remission, the disease relapsed 6 months later, and the patient eventually died 16 months following the diagnosis. Plasma cell leukemia is a rare hematological malignancy with a poor prognosis. The treatment has not been standardized yet. The present case suggested the effectiveness of the combination of hyper-CVAD and high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. Nevertheless, because of the short remission duration, intensification using tandem high-dose chemotherapy or maintenance using new agents such as bortezomib and thalidomide should be considered for improving the prognosis.