The Centers for Disease Control (CDC) testing recommendations suggest universal opt-out testing in all health care settings, including cancer clinics. The incidence of non-AIDS-defining cancers (NADCs) is on the rise among HIV patients. However, to date, no data exist on the prevalence of HIV infection among NADC patients in the United States. Knowledge of HIV infection may affect clinical management, prognosis, and overall patient survival and decrease new infections in the population. The purpose of this study was to determine the point seroprevalence of HIV infection in cancer patients being seen in medical oncology clinics. A total of 634 individuals (mean age=53.2 years) participated and were tested for HIV. None of the participants tested positive for HIV in any of the three clinics. Using a futility analysis, the upper end of the 95% confidence interval for prevalence of undiagnosed HIV in cancer patients was less than 0.3%. Most participants were female (59.2%) and non-Hispanic (96.6%). The majority of study participants were white (76.5%) or African-American (17.7%). Breast cancer (19.7%), colon cancer (10.3%), and melanoma (9.7%) were the most commonly reported non-AIDS-defining cancers. While our study suggested that there was no occurrence of undiagnosed HIV among NADC patients, it is important to note that our population was largely white, females with insurance and with a different distribution of cancer than the most prevalent NADC among HIV patients. Furthermore, one-third of the patients did not consent to participate and further studies are needed to assess reasons for their unwillingness along with other populations, specifically minorities and individuals with low socioeconomic status (SES). © Mary Ann Liebert, Inc.