The goal of the study was to determine the incidence and variables associated with post-liver transplantation (LT) de novo internal neoplasms development, excluding skin tumors and hepatocellular carcinoma. Medical records were reviewed for recipient/donor demographics, viral serology, cause of liver disease, interval from LT to tumor diagnosis, predisposing factors, immunosuppression and survival. Forty-one neoplasms (31 solid and 10 hematologic) developed in 772 recipients (5.3%) transplanted between 1991 and 2001. Time to tumor diagnosis was longer in patients transplanted before 1995 than in those transplanted afterwards (58 vs. 22 months; p < 0.05). Hematologic neoplasms (HN) appeared earlier than solid (2 vs. 21 months; p < 0.001), were more prevalent in those transplanted after 1995 than before (32% vs. 12.5%), and had lower survival than solid (2 vs. 21 months, p < 0.001). While HCV was the most frequent indication in HN (70%), alcohol was that of solid tumors (71%). Overall, risk factors for de novo neoplasms included alcohol and immunosuppression (p < 0.01). In patients undergoing LT in recent years, there is a higher incidence of HN with de novo internal neoplasms developing at earlier time-points than in those transplanted years ago. Risk factors for tumor development include alcohol, HCV and possibly strong immunosuppression.