We describe four patients with Crosti's lymphoma, a non-Hodgkin's B-cell lymphoma of follicular centre origin, treated with intralesional natural interferon alpha (IFN). In all patients the lesions cleared. Two patients had a clinical relapse but their lesions cleared after a second course of therapy. Intralesional injections are thought to have a direct action on tumoral cells as well as a systemic effect. Given the high rate of relapse after radiotherapy (75%), natural IFN is a promising therapeutic alternative.