The study aimed to evaluate the validity of a two-question case-finding instrument for depression compared to six other validated instruments. The two questions, which assess depressed mood and anhedonia, were administered to 536 consecutive adult patients in an urgent care clinic at the San Francisco Department of Veterans Affairs Medical Center. The prevalence of depression, determined by a standardized interview, was 18%. The two-question instrument had a sensitivity of 96% and a specificity of 57%, with similar areas under the receiver operating characteristic (ROC) curves to other instruments (0.82 to 0.89). The two-question instrument was more time-efficient and had comparable test characteristics to other instruments. The study concluded that the two-question instrument is a useful and efficient tool for detecting depression in primary care settings.The study aimed to evaluate the validity of a two-question case-finding instrument for depression compared to six other validated instruments. The two questions, which assess depressed mood and anhedonia, were administered to 536 consecutive adult patients in an urgent care clinic at the San Francisco Department of Veterans Affairs Medical Center. The prevalence of depression, determined by a standardized interview, was 18%. The two-question instrument had a sensitivity of 96% and a specificity of 57%, with similar areas under the receiver operating characteristic (ROC) curves to other instruments (0.82 to 0.89). The two-question instrument was more time-efficient and had comparable test characteristics to other instruments. The study concluded that the two-question instrument is a useful and efficient tool for detecting depression in primary care settings.