Over the last 30 years, the increasing use of organ and stem cell transplantation and the AIDS epidemic have led to the realization that some, but not all, human cancers occur more frequently in immunosuppressed individuals. With the notable exception of non-melanoma skin cancer (NMSC), most tumors that show strongly increased incidence rates in both transplant recipients and AIDS patients have been found to have a viral etiology. Among these are Kaposi sarcoma, diffuse large cell B-cell lymphoma, cervical cancer, liver cancer, Merkel cell carcinoma and a subset of Hodgkin's disease. A viral etiology for NMSC, i.e., beta- and gamma-subtypes of human papillomavirus, has been suggested and investigated for many years, but remains controversial. In addition, the moderately increased incidence rates of several other cancers in immunosuppressed individuals (e.g., Vajdic and van Leeuwen, Int J Cancer, in press) could indicate that additional infectious causes for at least some human cancers remain to be discovered. The controversy surrounding the role of cutaneous papillomavirus subtypes in the pathogenesis of NMSC illustrates the difficulties encountered when weighing the epidemiological and molecular biology evidence arguing for an involvement of highly prevalent viruses in certain types of cancer.