The acquired immunodeficiency syndrome (AIDS) results in an extraordinary increase in the risk of two malignancies: Kaposi's sarcoma (KS; relative risk [RR], >10,000) and B-cell non-Hodgkin's lymphoma (NHL; RR, >100). KS appears to result from uncontrolled expression of latency genes of human herpes virus-8 (HHV-8). KS is exquisitely sensitive to immune deficiency, and its incidence has declined during the late 1990s with the advent of highly active antiretroviral therapy (HAART) against human immunodeficiency virus (HIV). The risk of NHL is highest with high-grade histologies, and the incidence has declined only slightly with HAART. The risk of KS and NHL is decreased for people with the CCRS delta32 polymorphism, and NHL risk is increased with the SDFI-3'A polymorphism. Children with AIDS have a similar pattern of risk, but also have a high risk of leiomyosarcoma (RR, approximately 10,000). AIDS-related immune deficiency also increases the risk of Hodgkin's disease (RR, 8), probably multiple myeloma (RR, 5), and possibly other tumors in adults. Although the occurrence of cervical cancer (RR, 3) and anal cancer (RR, 30) is excessive among persons with AIDS, most or all of this excess results from sexually acquired human papillomavirus (HPV) infection and not from immune deficiency. Future efforts need to focus on understanding how the immune perturbation of AIDS results in a limited spectrum of tumors and most urgently on controlling the underlying HIV epidemic.