We report two cases of CHOP-resistant mediastinal diffuse large B-cell lymphoma (MDLCL) treated by autologous peripheral blood stem cell transplantation (auto-PBSCT). The patients were 17 and 28 year old female, and they had anterior mediastinal bulky masses at presentation. The clinical stage was IV in both patients. They were initially treated with 6 courses of bi-weekly CHOP therapy following by irradiation of the mediastinal tumors. During the last few cycles of CHOP therapy, their disease had become progressive. They underwent auto-PBSCT after high-dose chemotherapy consisting of busulfan, cyclophosphamide and etoposide, but failed to achieve remission. They died within one year after the auto-PBSCT because of the disease progression. Our experience suggests that this conditioning regimen is not effective for CHOP-resistant MDLCL, and it is necessary to develop new conditioning regimens.