[Show abstract][Hide abstract] ABSTRACT: Subcutaneous panniculitis-like lymphomas (SPTCLs) are a heterogeneous group of diseases characterized by pleomorphic lymphocytes infiltrating the subcutis in a lobular panniculitis-like pattern. Characterization of SPTCL based on T-cell phenotype has prognostic significance in that most patients with the alpha/beta T-cell phenotype of SPTCL demonstrate clinically indolent behavior, whereas those with gamma/delta variant typically manifest more aggressive disease. In the past, traditional therapies have included single-agent or systemic multi-agent chemotherapy with or without radiation therapy, immunosuppressive therapies, or, in refractory patients, bone marrow transplantation. We describe complete clinical regression of disease and a median response duration of > 6 months in 2 patients with SPTCL treated with corticosteroids and denileukin diftitox. Furthermore, the addition of bexarotene to denileukin diftitox restored a clinical response in 1 of the patients after disease progression, suggesting the activity of this combination in patients with SPTCL.