After highly active antiretroviral therapy (HAART) became widespread, several studies demonstrated changes in the incidence of defining and non-defining AIDS cancers among HIV/AIDS patients. We conducted a systematic review of observational studies evaluating the incidence of malignancies before and after the introduction of HAART in people with HIV/AIDS. Eligible studies were searched up to December 2012 in the following databases: Pubmed, Embase, Scielo, Cancerlit and Google Scholar. In this study, we determined the cancer risk ratio by comparing the pre- and post-HAART eras. Twenty-one relevant articles were found, involving more than 600,000 people with HIV/AIDS and 10,891 new cases of cancers. The risk for the development of an AIDS-defining cancer decreased after the introduction of HAART: Kaposi's sarcoma (RR = 0.30, 95% CI: 0.28–0.33) and non-Hodgkin's lymphoma (RR = 0.52, 95% CI: 0.48–0.56), in contrast to invasive cervical cancer (RR = 1.46, 95% CI: 1.09–1.94). Among the non-AIDS-defining cancers, the overall risk increased after the introduction of HAART (RR = 2.00, 95% CI: 1.79–2.23). The incidence of AIDS-defining cancers decreased and the incidence of non-AIDS-defining cancers increased after the early use of HAART, probably due to better control of viral replication, increased immunity and increased survival provided by new drugs.