Organ transplant recipients are considered to be at greater risk for developing malignancy because of the prolonged immunosuppression associated with organ grafting. The purpose of this study is to determine risk factors, clinical characteristics, and outcomes of de novo nonlymphoid malignancies after liver transplantation from a large single-center series. All patients undergoing liver transplantation at the King's College Hospital (London, UK) between January 1988 and December 1999 were analyzed retrospectively for the development of de novo malignancy in the posttransplantation period. Records were evaluated for age at diagnosis of malignancy, cause of liver disease, interval from transplantation to diagnosis of malignancy, predisposing factors for the development of cancer, immunosuppression regimen, treatment of malignancy, rejection episodes, and patient survival. Of 1,140 patients undergoing 1,271 liver transplantations, 30 patients (2.6%) developed de novo nonlymphoid malignancy after transplantation. Skin cancers were the most common (n = 13), followed by oropharyngeal carcinoma (n = 2), bladder carcinoma (n = 2), acute leukemia (n = 2), breast carcinoma (n = 2), and various other malignancies (n = 9). The mean time of presentation of the malignancy after transplantation was 45.1 +/- 32 months (range, 6 to 133 months), and mean age at diagnosis of malignancy was 55 years (range, 34 to 71 years). The incidence of de novo malignancy was significantly greater in patients who underwent transplantation for alcoholic liver disease compared with other groups (P <.001). Although the incidence of de novo nonlymphoid malignancy after liver transplantation is low, patients who underwent transplantation for alcoholic cirrhosis appear to have an increased risk for developing posttransplantation malignancy.