Iatrogenic immunosuppression is a unique setting for investigating immune-related mechanisms of carcinogenesis. Solid organ transplant recipients have a 3-fold excess risk of cancer relative to the age- and sex-matched general population. Population-based studies utilizing cancer registry records indicate that a wide range of cancers, mostly those with a viral etiology, occur at excess rates. To date, cancer risk has predominantly been examined in adult kidney transplant recipients in Western countries. It is yet to be established whether a similar incidence profile exists in the long-term for other solid organ, pediatric and non-Western transplant recipients. The cancer incidence profile before and after kidney transplantation strongly suggests a relatively minor contribution by both preexisting cancer risk factors and the conditions underlying end-stage kidney disease, and points to a causal role for immunosuppression. Within-cohort risk factor analyses have largely been performed on cohorts with voluntary cancer notification, and very few have incorporated biomarkers of the level of immunosuppression, the current receipt of immunosuppressive agents, or genetic risk factors. Because of their markedly high risk of certain cancers, findings from comprehensive studies in transplant recipients have the potential to raise new avenues for investigation into causal mechanisms and preventive measures against immune-related and infectious causes of cancer.