Recombinant interferon alpha (r IFN alpha) has shown significant antitumor activity in patients with follicular small cleaved cell (low-grade non-Hodgkin's lymphomas) and cutaneous T-cell lymphomas. However, IFN alpha seems to be less effective in patients with intermediate or high-grade lymphomas. This case report describes a patient with an initial diagnosis of low grade B-cell lymphoma with histologic conversion to diffuse large B-cell (B1+, Kappa+) cutaneous lymphoma. This tumor proved refractory to chemotherapy but a complete and durable remission was induced with R IFN alpha 2a treatment.