A 26-year-old woman with acute lymphoblastic leukemia (ALL) relapsed three times after HLA-matched related bone marrow transplantation. Initially, ALL relapsed in the central nervous system (CNS) 1 year after transplantation. Then, ALL relapsed as a single bone tumor involving the CNS and pelvis 4 years after transplantation. Finally, multiple bone tumors in the pelvis and lumbar bones were found as well as spread to the bone marrow 5 years after transplantation. Bone marrow aspiration also showed ALL relapse. Flow cytometry analyses detected CD20-positive cells in the bone tumor. Though the initial bone tumor was resistant to hyper CVAD, radiation was effective and this patient achieved complete remission. At that time, the total radiation dose had already reached the upper limit. After the third relapse, bone marrow achieved complete remission with the administration of pirarubicin, vincristine, prednisolone, and L-asparaginase (arranged DVP-L), though this combination chemotherapy itself was not effective in multiple bone tumors. Thereafter, arranged DVP-L plus rituximab was administered, which resulted in significant tumor reduction. Biweekly rituximab administration as maintenance therapy has completely prevented the regrowth of bone tumors. Rituximab for relapsed CD20-positive ALL patients after stem cell transplantation could be beneficial.