Background: The objective of this study is to evaluate the incidence of non-AIDS defining malignancies (NADMs) among people living with HIV/AIDS (PLWHA) in British Columbia, focusing on clinical correlates, highly active antiretroviral therapy (HAART) use, and survival, in order to elucidate mechanisms for NADM development. Methods: A retrospective population based analysis was carried out for individuals with HIV/AIDS that began their treatment between 1996 and 2008. Results: There were 145 (2.95%) NADMs and 123 (2.50%) AIDS defining malignancies (ADMs) identified in 4918 PLWHA in the study population. NADMs were represented by a range of cancer types including, most commonly, lung cancer, followed by anal, breast, head/neck, prostate, liver, rectal, and renal cancers. PLWHA had a SIR of 2.05 (CI: 1.73, 2.41) for the development of NADMs compared to individuals without an HIV/AIDS diagnosis in the general population. Independent factors significantly associated with a NADM were: male gender, older age, lower CD4 cell counts, previous NADM, absence of HAART (non-HAART versus HAART) and treatment during the early-HAART era (before 2000 versus after 2000). Conclusions: NADMs represent an important source of morbidity for PLWHA. Use of HAART with its associated improvement in immune-restoration, and tailored targeted cancer screening interventions, may be beneficial and improve outcomes in this unique patient population.