Through this Notice of Special Interest (NOSI), the National Cancer Institute (NCI) intends to continue advancing our understanding of the risks, development, progression, diagnosis, and treatment of malignancies observed in individuals with an underlying human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), which are now a leading cause of death in people with HIV (PWH). This NOSI calls for proposals that seek to identify specific contributions of HIV infection and its potential interaction with other oncogenic pathogens on the development and pathogenesis of these cancers, including studies that provide new information on the clinical outcomes of such cancers in the HIV-infected population. Ultimately, such efforts could guide development of targeted screening approaches and therapies optimized for PWH. AIDS research as described in the Office of AIDS Research (OAR) priorities is encouraged in areas such as the study of the etiologic factors, cofactors, immunopathogenesis, diagnosis, and outcomes of cancer in populations with an underlying HIV infection. The purpose of this NOSI is therefore aligned with OAR priorities for AIDS research and is specifically launched to foster cancer-focused research that addresses important gaps in knowledge for the control and treatment of cancer and cancer-related comorbidities among PWH.