Mental illness and substance abuse are common among HIV-infected individuals and are associated with negative outcomes, including poor medication adherence. Therefore, quick and effective methods for detecting these co-occurring disorders are necessary for health care practitioners. This article reports on the creation and preliminary testing of a brief screening tool, the Substance Abuse and Mental Illness Symptoms Screener (SAMISS). The 13-item screener was developed primarily from existing scales and administered to HIV-infected individuals receiving care at infectious diseases clinics in the Southeast. To assess the validity of the SAMISS, a subset of those who screened positive for both mental illness symptoms and substance use problems (n = 207) were administered the Structured Clinical Interview for DSMIV Disorders (SCID). The positive predictive value of the screener in comparison to the SCID was 98.6% for mental disorders and 98.6% for substance use disorders. The agreement between specific screener symptoms and their corresponding SCID diagnoses was relatively high for alcohol dependence (kappa = 0.50, p < 0.001), drug dependence (kappa = 0.30, p < 0.001), and drug abuse (kappa = 0.42, p <0.001). The finding that the screener is highly predictive of having a general mental disorder and substance use disorder among those screening positive for mental illness symptoms and substance use problems, as well as its brevity and ease of administration, make it a useful tool to detect symptoms of co-occurring disorders so that patients can be referred to mental health and substance abuse specialists. The screener is not a diagnostic instrument and has limited value in predicting specific psychiatric diagnoses.