Photopheresis is being used with increasing frequency as therapy for patients with neoplastic and dermatologic diseases and is being evaluated as therapy for patients with AIDS. We describe a patient with advanced cutaneous T cell lymphoma who developed pulmonary and cutaneous cryptococcosis after receiving therapy with photopheresis and biweekly methotrexate. We consider the potential roles of cutaneous T cell lymphoma, methotrexate, and photopheresis as predisposing factors in the development of serious cryptococcal infections.