Recent studies emphasize the negative impact of comorbidity on the course of depression. If undiagnosed, depression and comorbidity contribute to high medical utilization. We aimed to assess (1) prevalences of depression alone and with comorbidity (anxiety/somatoform disorders) in primary care, (2) coexistence of anxiety/somatoform disorders in depressive patients, and (3) diagnostic validity of two screeners regarding depression with versus without comorbidity. We examined 394 primary care outpatients using the Composite International Diagnostic Interview (CIDI), the General Health Questionnaire (GHQ-12), and the Well-Being Index (WHO-5). We conducted configurational frequency analyses to identify nonrandom configurations of the disorders and receiver operating characteristic (ROC)-analyses to assess diagnostic validity of the screeners. Point prevalence of any depressive disorder was 22.8%; with at least one comorbid disorder, 15%; and with two comorbid conditions, 6.1%, which significantly exceeded expected percentage (0.9%, P< or =.0001). Depression without comorbidity occurred significantly less often than expected by chance (P< or =.0007). Comorbidity of depressive and anxiety or somatoform disorders was associated with a high odds ratio (6.25). The screeners were comparable regarding their diagnostic validity for depression with [GHQ-12: area under the curve (AUC)=0.86; WHO-5: AUC=0.88] and without comorbidity (GHQ-12: AUC=0.84; WHO-5: AUC=0.86). It can be concluded that comorbidity between depression and anxiety/somatoform disorders in primary care may occur much more frequently than expected. These results confirm assumptions that the current division between depression and anxiety might be debatable. Validity of screeners tested in our study was not affected by comorbid conditions (e.g., anxiety or somatoform disorders).