De novo tumors (DNT) are a serious complication after orthotopic liver transplantation (OLT), showing a higher overall incidence ranging from 4.7% to 15.7% in non-selected series. Skin cancer (SC) is the most frequent malignancy observed, ranging from 6% to 70% of the tumors observed, followed by post-transplant lymphoproliferative disorders (PTLD) (4.3-30%). Different immunosuppressive protocols do not seem to influence DNT appearance. Colon and upper aerodigestive cancer after OLT seems to be more prone to develop when there are associated risk factors, such as primary sclerosing cholangitis (PSC) and alcoholic liver cirrhosis (ALC). Some risk factors, such as age, smoking, alcohol and others seem to play a role in higher risk for malignancy, but the presence of a long-term immunosuppressive state, more than the specific regimen used, is the basis for this higher incidence. Ethnic and demographic factors are also important variables influencing the heterogeneity of the results, especially influencing Kaposi's sarcoma and skin tumors.