The aims of this analysis are to characterize the incidence and types of malignancies and tumor-specific mortality in our institution. Retransplantation, rejection episodes, and OKT3 use were evaluated. Our single-institution prospective database of 1,570 liver transplantations in 1,421 patients was analyzed. Data were statistically analyzed regarding sex, age at transplantation, time from transplantation to diagnosis of tumor, tumor type, and follow-up time. One hundred twenty-five patients (8.8%) developed de novo tumors; 69 patients were men, 56 patients were women. Seventeen patients received more than one allograft. De novo tumors were as follows: skin, 41; lymphomas, 35; lung, 11; colon, 6; anal, 2; rectal, 1; breast, 7; thyroid, 3; oropharyngeal squamous cell, 3; metastatic without primary tumor identified, 4; renal cell, 3; Kaposi's sarcoma, 1; angiosarcoma, 1; uterine, 1; ovarian, 1; pituitary, 1; pancreatic, 2; cholangiocarcinoma, 1; and esophageal, 1. These tumors developed in a statistically significant chronological sequence. Lung cancers and lymphomas showed shorter mean survival times, as well as greater mortality. OKT3 use and rejection did not show significance in tumor development. De novo tumors post–liver transplantation affected our population in a distribution similar to that of the general nontransplantation population. Intense short courses of immunosuppression for rejection were not as important as chronic immunosuppression in the development of tumors. The risk for development was not enough to preclude transplantation. We found that tumors developed in chronological fashion. Therefore, directed surveillance, patient education, and early detection may facilitate earlier treatment.