The risk of developing malignancy is higher in patients with human immunodeficiency virus (HIV) infection than in non-HIV-infected patients. Several factors including immunosuppression, viral coinfection, and high-risk lifestyle choices lead to higher rates of cancer in the HIV-infected population. A subset of HIV-related malignancies are considered to be acquired immunodeficiency syndrome (AIDS)-defining malignancies, as their presence confirms the diagnosis of AIDS in an HIV-infected patient. The introduction of highly active antiretroviral therapy (HAART) has led to a significant drop in the rate of AIDS-defining malignancies, including Kaposi sarcoma, non-Hodgkin lymphoma, and invasive cervical carcinoma. However, non-AIDS-defining malignancies (eg, Hodgkin lymphoma, lung cancer, hepatocellular carcinoma, and head and neck cancers) now account for an increasing number of cancer cases diagnosed in HIV-infected patients. Although the number has decreased, AIDS-defining malignancies account for 15%-19% of all deaths in HIV-infected patients in the post-HAART era. Most HIV-related malignancies in HIV-infected patients manifest at an earlier age with a more aggressive course than that of non-HIV-related malignancies. Understanding common HIV-related malignancies and their specific imaging features is crucial for making an accurate and early diagnosis, which impacts management. Owing to the weakened immune system of HIV-infected patients, other entities such as various infections, particularly opportunistic infections, are prevalent in these patients. These processes can have confounding clinical and imaging manifestations that mimic malignancy. This article reviews the most common AIDS-defining and non-AIDS-defining malignancies, the role of imaging in their diagnosis, and the imaging mimics of malignancies in HIV-infected patients. ©RSNA, 2018.