Few data are available regarding the 10-year survival among subjects with HIV and cancer. The aim of this study was to evaluate the 10-year survival of HIV-infected subjects with AIDS-defining malignancies (ADM) or non-AIDS-defining malignancies (NADM). This was a single center, retrospective, observational study of subjects with HIV infection and a subsequent cancer diagnosis; the data were collected from January 1991 to April 2010. Malignancies were divided into ADM or NADM on the basis of the Centre of Diseases Control-1993 classification. Survival curves were estimated using Kaplan–Meyer method and compared by the log-rank test. Six hundred and fifteen (9.5%) of the 6,495 subjects recorded in the San Raffaele Infectious Diseases Database developed a malignancy: 431 (70%) an ADM and 184 (30%) a NADM. In the case of ADM, survival was more favorable when cancer was diagnosed during post-highly active antiretroviral therapy (HAART) era (10-year survival: 43.2% ± 4.4%) than when diagnosed during the pre-HAART era (10-year survival: 16.4% ± 2.7%; log-rank test: p < 0.001). The same was true in the case of NADM (10-year survival: 44.7% ± 5.5% vs. 33.3 ± 9.6%; log-rank test: p = 0.03). An evaluation of survival probability by cancer type showed higher survival rates during the post-HAART era in the case of non-Hodgkin lymphoma (10-year survival: 42.1% ± 5.3% vs. 11.4% ± 3.3%; log-rank test: p = <0.001), Kaposi's sarcoma (10-year survival: 44.0% ± 8.4% vs. 23.5% ± 3.9%; log-rank test: p < 0.001) and Hodgkin's disease (10-year survival: 49.5% ± 14.5% vs. 40.0% ± 12.7%; log-rank test: p = 0.005). Despite the better cancer prognosis during the post-HAART era, the 10-year survival of HIV-infected subjects with an ADM or NADM is poor.