This study aimed to assess the reliability, validity, and factor structure of the Greek translation of the Patient Health Questionnaire (PHQ) in a sample of Cypriot, Greek-speaking university students. This is the first study to examine PHQ psychometric properties in Greek and to investigate the factor structure of the PHQ subscales. A total of 520 participants (73.9% women; M(Age) = 21.57; SD, 4.94) completed the PHQ and assessment tools used for convergent validity analysis. Patient Health Questionnaire was translated and culturally adapted according to international standards. Overall, PHQ subscales in Greek language demonstrated good internal consistency (mean Cronbach α = .75, P < .001) and convergent validity with the following: Alcohol Use Disorders Identification Test, Beck Depression Inventory, Psychiatric Diagnostic Screening Questionnaire (panic disorder, somatization, bulimia, and binge eating), and Anxiety Sensitivity Index (overall mean, r = 0.52; P < .001). The relation between the PHQ subscale diagnoses and functional impairment, as assessed by the 12-item Health Survey 12, was comparable with the original validation results for all subscales except alcohol. The depression, alcohol, and anxiety subscales exhibited single-factor structures. Subscales assessing eating disorders, panic disorder, and somatization difficulties exhibited 2-, 3-, and 4-factor structures, respectively. Overall, PHQ subscales demonstrated good psychometric properties, with the exception of the subscale examining problematic alcohol use. Overall, PHQ demonstrates good reliability, validity, and appropriate factor structure in a Greek-speaking college population. Psychometric research is needed on the Greek PHQ in primary care settings.