An increased incidence of de novo malignancies in immunocompromised patients was first predicted by Professor Thomas Starzl and coworkers in 1968 and was confirmed shortly afterwards by others. The immunocompromised state provides a permissive environment for malignant cells to grow, for an oncogenic virus to infect or reactivate within the host, for chronic antigen stimulation leading to a cytokine-rich milieu, and for impaired immune surveillance imposed by chronic immunosuppression. With the increasing success of liver transplantation (LTx) and fewer episodes of acute rejection with virtual freedom from chronic rejection, long-term survival rates have improved. In addition, with an aging population, older recipients are also being considered for LTx. Currently, long-term graft loss and death are not commonly related to rejection but are often due to age-related complications, such as cardiovascular disease and de novo cancers. The rate of de novo cancers after LTx has been reported to range from 3% to 26%, and the variation is partly due to the length of follow-up, different ways of reporting, and geographic variations in de novo malignancies. Although registry data of de novo cancers provide a valuable source for accounting for the various types of malignancies; these registries do not include the denominator of the population at risk. The cumulative number of years of follow-up is also unknown, and this makes it difficult to calculate the actuarial risk. In this respect, data from single centers with long-term follow-up have become an important source of information for the incidence and nature of de novo cancers, which can then be compared with surveillance epidemiological end results data. Furthermore, these data can be presented as a standard incident ratio (SIR). Also, the incidence of de novo cancers can be evaluated on the basis of the number of person years post-transplantation; the cumulative actual survival of patients after transplants is included until the last follow-up or time of death. Within the published literature, there are significant inconsistencies in the reporting of de novo malignancies. For example, some authors prefer to include posttransplant lymphoproliferative disorders (PTLDs) along with de novo solid cancers, whereas others prefer not to include them. This has caused a major discrepancy in reported rates of de novo cancers. Nonmelanoma, non-Kaposi’s skin cancers (squamous cell cancer and basal cell carcinoma) are the commonest types of de novo malignancies in the posttransplant population, with an up to 70 times higher incidence in comparison with nontransplant populations. One way to report this is to separate lymphoid lesions from nonlymphoid cancers and then separate the nonlymphoid cancers. Even after stratification of lymphoid and nonlymphoid cancers in this manner, there appears to be a wide variation in the different types of de novo cancers.