Individuals infected with human immunodeficiency virus (HIV) have a greater risk of developing malignancies, including both acquired immunodeficiency syndrome (AIDS)-defining malignancies as well as many non-AIDS-defining cancers. Several factors contribute to the increased incidence of malignancies in this population such as the direct effects of HIV itself, immune deficiency, co-infection with oncogenic viruses, environmental factors, and the effects of combination antiretroviral therapy (cART). The improvement of the immune response following the introduction of cART results in a better response to conventional therapies for malignancies, including chemotherapy, radiotherapy, and surgery. Significant disparities still exist in cancer treatment for people living with HIV and afflicted with cancers compared to those without HIV, with many in the former group not receiving any cancer treatment at all. We report a rare case whereby a newly diagnosed HIV-infected patient with Epstein-Barr virus-positive diffuse large B-cell lymphoma showed spontaneous regression of the lymphoma with the introduction of cART alone without any treatment of the cancer itself. We reviewed similar cases described in the literature and examined the possible explanations for this phenomenon.