Interferon (IFN) treatment is a therapeutic option in the treatment of non-Hodgkin's lymphoma (NHL). Although randomized trials have failed to show significant differences in progression-free and overall survival (OS) with IFN compared to placebo after peripheral blood stem cell transplantation (PBSCT) as well as standard therapy for NHL, anecdotal case reports have documented impressive results in selected patients. With this case report, we demonstrate an astounding success of IFN therapy given in the treatment of a young man with second relapse after two consecutive autologous PBSCTs and abdominal irradiation. With occurrence of multiple lymph node enlargements despite this intensive treatment, he received IFN and obtained a well-documented complete remission (CR). Yet, treatment with IFN always has to be considered in the context of its significant side effect profile, which can have considerable impact on the patient's quality of life as illustrated in this case report.