Problem: Since the introduction of highly active antiretroviral therapy (ART), the incidence rates of non-AIDS defining malignancies (NADMs) has steadily increased in the HIV-seropositive population. In the post-ART era, the incidence rates of several NADMs are now higher in HIV-seropositive individuals than in the general population. In addition to having an elevated risk of acquiring NADMs, once diagnosed, HIV-seropositive individuals have significantly poorer survival rates when compared to the general population, despite having similar life expectancies prior to a NADM diagnosis. As ART uptake becomes more widespread and the HIV-seropositive population continues to age, the incidence and mortality due to NADMs in this population will continue to increase. Goal: To improve survival among the HIV-seropositive population. Purpose: To identify the factors that affect survival among individuals diagnosed with comorbid HIV and cancer. Methods: We conducted three retrospective cohort studies using South Carolina HIV/AIDS, cancer, and healthcare utilization registry data. First, we compared the survival of HIV-seropositive individuals to HIV-seropositive cancer cases to better define the impact that a cancer diagnosis has on survival. Second, we compared HIV-seropositive cancer cases to an HIV-seronegative cancer comparison group to determine how a previous HIV infection affects survival among cancer patients, and whether this is modified by malignancy characteristics. Third, we compared healthcare utilization between HIV-seropositive individuals and HIV-seropositive cancer cases to determine if healthcare utilization impacted the likelihood of developing cancer or subsequent survival. Results: Receiving a cancer diagnosis had a profound effect on the survival of HIV-seropositive individuals (hazard ratios (HR) ranging from 7 to 67), with individuals with HIV only (i.e., no AIDS diagnosis) affected the most. When compared to an HIV-seronegative cancer comparison group, a previous HIV infection significantly affected survival among individuals diagnosed with NADMs (HR: 1.6). The effect of HIV was greatest among individuals diagnosed with lower stage tumors and those with higher survival expectancies. HIV-related healthcare utilization had no impact on survival when controlling for other covariates. Conclusions: Cancer significantly impacts survival among HIV-seropositive individuals, particularly among individuals with otherwise high survival expectancies.