Background: Psychiatric disorders are frequent in dermatology patients, and many studies pointed out complex, mutual relationships between psyche and skin. Our aim was to provide a systematic psychosocial evaluation of a large and heterogeneous population of patients with skin diseases, including assessments of quality of life, psychiatric status according to the DSM-IV and psychological conditions with psychosomatic relevance according to established criteria (Diagnostic Criteria for Psychosomatic Research, DCPR). Methods: We studied 545 dermatological inpatients aged 18–65 years, free from dementia and cognitive impairment. They completed the Skindex-29 and the 12-item General Health Questionnaire (GHQ-12) and were administered the SCID-I and the Structured Interview for Psychological Conditions of Psychosomatic Relevance by a trained mental health professional blinded to questionnaire scores. Results: Overall, 38% of patients received a DSM-IV diagnosis. The most common diagnoses were mood (20%) and anxiety disorders (16%); 48% of patients also received a DCPR diagnosis. The most common were demoralisation, irritable mood, type A behaviour and various forms of abnormal illness behaviour. Adjusting for gender, age, and education, the presence of DSM-IV or DCPR diagnoses was significantly associated with high scores on the GHQ-12 and on the Functioning and Emotions scales of the Skindex-29. Also, DCPR diagnoses were significantly associated with high scores on the Symptoms scale of the Skindex-29. Conclusions: These findings highlight the high frequency of psychosocial problems in patients with skin disease and suggest that the joint use of DSM-IV and DCPR criteria may help identify those patients in whom psychiatric issues are worthy of increased clinical attention.