Donor-derived melanoma is easily transmitted through organ transplants and is highly aggressive in transplant recipients. The best treatment-withdrawal or reduction of immunosuppression-permits tumor rejection but risks allograft rejection. In recipients of nonrenal allografts, the prognosis is particularly grim, with transmission rates and mortality approaching 100%. Retransplantation has been proposed as a possible strategy but has never been performed for a cardiac allograft. This is the first report of cardiac retransplantation and only the second case of retransplantation of any nonrenal organ. Our patient received a heart transplant from a donor found to have occult metastatic melanoma at autopsy. He underwent retransplantation 17 days later. Close clinical and radiographic follow-up reveal no evidence of melanoma 22 months after transplantation. Based on the rapid development of donor-derived melanoma in previous reports, our patient is likely to remain free of donor cancer. Retransplantation and low-dose immunosuppression may have been lifesaving.