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People with HIV are at an increased risk for both AIDS-defining and non-defining cancers. These can occur also after an initial cancer diagnosis as either first or second primary cancers. This study used the San Francisco HIV/AIDS Case Registry with data from 1990 to 2010. These data were matched with the California Cancer Registry, and 4545 incident primary cancers were identified. Standardized incidence rates were calculated to allow comparisons. Not surprisingly, ratios for HIV-associated cancers, such as Kaposi sarcoma, non-Hodgkin’s lymphoma, and anal cancer were higher for both primary and secondary cancers in persons with HIV and an initial cancer diagnosis. However, lower first primary cancer incidence ratios for prostate cancer, colon cancer, and pancreatic cancer, and lower secondary prostate cancer incidence ratios were observed. Other findings of less prostate cancer in persons with HIV have been reported without a clear explanation. Because of the risk of primary and secondary cancers after an initial cancer diagnosis, prevention, screening, and treatment of cancers are clearly indicated in such persons with HIV.