The recognition of comorbidity has important clinical significance. Comorbidity predicts a poorer outcome for patients with depressive and anxiety disorders, and the presence of multiple psychiatric disorders is associated with greater psychosocial impairment. In routine clinical settings, an unstructured interview is typically used to assess patients. However, unstructured interviews may result in missed diagnoses, with potential negative clinical consequences. The goal of the present study was to examine whether diagnostic comorbidity is less frequently identified during a routine clinical evaluation versus a semistructured diagnostic interview. Axis I diagnoses derived from structured and unstructured clinical interviews were compared in two groups of psychiatric outpatients in the same practice setting. Five hundred individuals presenting for an intake appointment to a general adult psychiatric practice underwent a routine unstructured clinical interview. Subsequent to completion of the first study, the method of conducting diagnostic evaluations was changed and 500 individuals were interviewed with the Structural Clinical Interview for DSM-IV Axis I Disorders (SCID). The two groups had similar demographic characteristics and scored similarly on symptom questionnaires. Individuals interviewed with the SCID were assigned significantly more axis I diagnoses than individuals assessed with an unstructured interview. More than one third of the patients interviewed with the SCID were diagnosed with three or more disorders, in contrast to fewer than 10% of the patients assessed with an unstructured interview. Fifteen disorders were more frequently diagnosed in the SCID sample, and these differences occurred across mood, anxiety, eating, somatoform, and impulse-control disorder categories. The results suggest that in routine clinical practice, clinicians underrecognize diagnostic comorbidity. Anxiety, somatoform, and not otherwise specified (NOS) disorders were the most frequently underdetected disorders. The implications of underdiagnosis for the treatment outcome are discussed.