Liver transplant recipients are at greater risk for de novo neoplasia, especially lymphoma and nonmelanoma skin cancer; however, risk factors for this complication have not been well studied. Clinical and pathological records of 137 consecutive liver transplant recipients who had survived for at least 1 year were reviewed to register de novo neoplasia. Ten variables were analyzed for their association with the development of de novo malignancies by means of a log-rank test and stepwise selection in a multivariate analysis using the Cox proportional hazard model. Thirty de novo neoplasias appeared in 22 of 137 transplant recipients between 12 and 104 months after orthotopic liver transplantation (OLT; median follow-up, 69 months): 14 patients had 21 skin cancers, 6 patients had solid-organ cancer, and 3 patients developed a lymphoproliferative disease. Probabilities of de novo neoplasia were 13% at 5 years post-OLT and 26% at 8 years post-OLT. The only associated risk factor for any neoplasia was age. Age and hepatocarcinoma were independent risk factors associated with skin cancer. That hepatocarcinoma in the explanted liver is an independent risk factor for skin cancer suggests there is individual susceptibility to both neoplasias.