PURPOSE OF REVIEW: The incidence and spectrum of non-AIDS-defining cancers has continued to grow. As HIV-infected individuals live longer due to highly active antiretroviral therapy, their risk of dying from one of these cancers is increased. The recent literature pertaining to non-AIDS-defining cancers is reviewed. RECENT FINDINGS: Recent epidemiological studies have identified higher rates of carcinoma of the anus, lung, breast, skin, conjunctiva, liver and prostate; hematopoietic malignancies such as Hodgkin's lymphoma, plasma-cell neoplasia and leukemia; and other neoplasms like melanoma and leiomyosarcoma in HIV-positive patients. The role of HIV-induced immunosuppression in the development of these non-AIDS-defining cancers appears less important than lifestyle habits like smoking and sun exposure, as well as coinfection with human papilloma, hepatitis B, hepatitis C and Epstein-Barr viruses. SUMMARY: It is unclear whether the growing number of reports on non-AIDS-defining cancers reflects a true increased incidence or merely the product of increased surveillance, detection and reporting. Highly active antiretroviral therapy not only promotes longevity in the HIV-positive population, but may increase their risk of developing cancer like Hodgkin's lymphoma. Assertive prevention strategies are needed to adequately deal with non-AIDS-defining cancers in an aging and growing HIV-positive population.