Background. As long-term survival after cardiac transplantation improves, neoplastic complications are increasingly being discovered. Although lymphoproliferative disorders predominate, the incidence and clinical spectrum of solid tumors in a uniform population of heart transplant recipients remains uncertain. Methods. We reviewed our experience with 712 patients who underwent cardiac transplantation. Clinical charts were reviewed and telephone interviews were conducted, when possible. Results. De novo solid malignancies were identified in 3.3% of patients at risk (21 of 633 patients). Twenty patients were male; mean age was 51.5 +/- 8.6 years. Most patients reported a significant smoking history. Pulmonary, urologic, and Kaposi's sarcoma were the most common malignancies identified. Mean interval from transplantation to diagnosis was 35 months. Six patients were diagnosed within 6 months of transplantation. One-year and 5-year survival after transplantation were 90% and 49%, respectively. One-year and 3-year survival after cancer diagnosis were 60% and 52%, respectively. Conclusions. De novo solid malignancy after transplantation occurred with about half the frequency of lymphoproliferative disorders. A striking male predominance was noted. The interval from transplantation to the appearance of cancer is variable, and no clustering was identified. A significant smoking history warrants aggressive search for occult malignancy during pretransplantation evaluation of potential heart recipients.