High-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (PBSCT) is beneficial for patients with relapsed or refractory but chemosensitive diffuse large B-cell lymphoma (DLBCL). However, most elderly patients are not indicated for that therapy and receive supportive treatment only. We describe here two elderly patients with relapsed or refractory DLBCL who achieved prolonged disease-free survival after undergoing intermediate-dose melphalan therapy supported by PBSCT (MEL100) three times. Case 1 was an early relapse (within one year) after the first remission and case 2 was a second relapse. Both cases are currently alive without relapse and have maintained a good performance status for 41 months and 32 months, respectively, after MEL100. Febrile neutropenia and herpes zoster as non-hematological toxicities (grade > or = 3) occurred only in case 1. Considering the benefits vs. toxic effects, this regimen may improve the prognosis of elderly patients with relapsed or refractory DLBCL by MEL100.