Highly active antiretroviral therapy (HAART) has dramatically reduced the incidence of acquired immunodeficiency syndrome (AIDS) and increased AIDS survival time, but little is known about its impact on cancer. Data from adults in the San Francisco, California, AIDS surveillance registry were computer matched with the California Cancer Registry. Age-, sex-, and race-adjusted standardized incidence ratios (SIRs) were computed, and proportional hazards models evaluated the effect of HAART use on cancer incidence and cancer survival time. Among 14,210 adults with AIDS diagnosed in 1990-2000, 482 non-AIDS-defining cancers were diagnosed. Compared with rates for the general population, significantly increased cancer incidence rates were observed for anal (SIR = 13.4), Hodgkin's lymphoma (SIR = 11.5), liver (SIR = 3.6), oral cavity and pharynx (SIR = 2.6), respiratory (SIR = 2.6), leukemia (SIR = 2.4), skin melanoma (SIR = 2.4), and prostate (SIR = 1.7) cancers. Risk of liver cancer was lower with HAART use (relative hazard (RH) = 0.32). Risk of anal cancer increased after 1995 (RH = 2.9). Respiratory cancer (RH = 0.40) and Hodgkin's lymphoma (RH = 0.17) showed increased cancer survival time with HAART use, while anal cancer survival may have been slightly decreased (RH = 1.4). The impact of HAART on non-AIDS-defining cancer incidence rates and survival is not uniform, and the mechanism(s) responsible for these differences should be investigated further.