Recent developments in cancer epidemiology have led to the possibility of an exceedingly complex communicable factor(s) in cancer etiology. The transmission of such an agent(s) may require a susceptible genotype and/or other promotional events. Likely candidates which support this supposition include: Epstein-Barr virus (nasopharyngeal carcinoma, Burkitt's lymphoma, salivary gland tumor among Eskimos, X-linked lymphoproliferative syndrome of Purtilo); human T-cell leukemia virus (adult T-cell leukemia); acquired immune deficiency syndrome (AIDS), complicated by Kaposi's sarcoma (etiologic agent remains elusive, though epidemiology suggests possible infectious transmission); abnormal immune phenomena in households of Hodgkin's disease patients; and clustering of various types of cancer in spouses, the general population, and families. We have selectively reviewed the literature and evolved an etiologic hypothesis which integrates a communicable agent(s) in concert with genetic and/or environmental carcinogenic interaction which could conceivably explain a significant fraction of the total cancer burden.