Together with cardiovascular disorders and metabolic changes, malignant diseases are considered as great challenges in clinical transplantation. As far as long-term function of transplanted organs is concerned, an impact of malignancies is obvious. However, it is important to distinguish between neoplastic disease originating from preexisting lesions in the transplanted organs and de novo graft tumors. Further, there is also a high risk of developing malignant disease during the dialysis, likely due to potential harmful metabolic changes associated with this procedure. After curative management of tumors in such patients, an interval of 2 years for surveillance should be adhered to before patients are put back on the waiting list. The overall risk of transmission of a malignant disease with the transplanted graft has been considered to be as low as <0.2%. In this context, and considering the continual shortage of donated organs, there is an international consensus about the use of kidney grafts with a history of small tumors (<2 cm in diameter und low-grade, i.e., G1). However, the lesions should have been removed with subsequent histopathologic characterization before the acceptance of the organ for transplantation. Early diagnosis and management of de novo malignant disease in transplant patients is crucial for the prognosis of graft function and patient survival. Genitourinary malignancies are frequent among de novo malignancies in transplanted patients. Thus, there is a need for clearly structured concepts for screening of transplant patients in order to detect early malignancies. The incidence of malignant disease correlates directly with the extent of immunosuppression in patients with end-stage renal disease (ESRD) on dialysis, as well as after transplantation with life-long immunosuppressant therapy. In addition, also geographic factors seem to play a role in the differential incidence of tumors among different populations. For instance, the highest incidence of malignancies among immunosuppressed patients has been observed in Australia followed by the USA and Europe. This might be due to the high incidence of de novo skin cancer, which has been linked to the extent of UV exposure.