Thrombotic thrombocytopenic purpura (TTP) is a critical complication of treatment with mitomycin C. We retrospectively describe the case of a patient with progressive renal cell carcinoma and mitomycin-induced TTP refractory to plasma exchange and glucocorticoids; we describe the clinical course, successful management of TTP with rituximab, and follow-up of this case. Mitomycin-induced TTP resolved completely by a total of 4 infusions of rituximab 375 mg/m(2) on a weekly basis, and it took up to 12 months to obtain a platelet count of >100,000/µL. Rituximab is indicated for the treatment of mitomycin-induced TTP refractory to plasma exchange and glucocorticoids, and it could improve the patient's quality of life despite the presence of underlying malignancy.