Itch is a highly prevalent and multidimensional symptom. We aimed to analyze the association between itch and mental health in dermatological patients. This multicenter study is observational and cross-sectional and was conducted in dermatological clinics across 13 European countries. A total of 3,530 patients and 1,094 healthy controls were included. Patients were examined clinically. Outcome measures were itch (presence, chronicity, and intensity), the Hospital Anxiety and Depression Scale, EQ-5D visual analogue scale, sociodemographics, suicidal ideation, and stress (negative life events and economic difficulties). Ethical approval was obtained. Results showed significant association between the presence of itch in patients and clinical depression (odds ratio, 1.53; 95% confidence interval, 1.15-2.02), suicidal ideation (odds ratio, 1.27; 95% confidence interval, 1.01-1.60), and economic difficulties (odds ratio, 1.24; 95% confidence interval, 1.10-1.50). The mean score of reported generic health status assessed by the EQ-5D visual analogue scale was 65.9 (standard deviation = 20.1) in patients with itch, compared with 74.7 (standard deviation = 18.0) in patients without itch (P < 0.001) and 74.9 (standard deviation = 15.7) in controls with itch compared with 82.9 (standard deviation = 15.6) in controls without itch (P < 0.001). Itch contributes substantially to the psychological disease burden in dermatological patients, and the management of patients should include access to multidisciplinary care.