Pemphigus is a rare autoimmune dermatological disease, whose onset and course depend on the interaction between predisposing severed and inducing factors. Psychological stress has been suggested to be a potential triggering factor of pemphigus. However, this hypothesis has not been thoroughly investigated. To this purpose, we explored recent stressful life events and personality disorders in 25 consecutive subjects with pemphigus. Baseline information was collected on demographic characteristics, family history, presence of psychopathology, the impact of stressful life events occurring within one year prior to onset of pemphigus, presence of Axis I and Axis II diagnosis, using standardized instruments. Patients affected by pemphigus were matched for number, age and gender with subjects with other skin diseases and with healthy volunteers. All pemphigus patients had a negative anamnesis for Axis I diagnosis. Pemphigus patients showed a significantly higher Comprehensive Psychopathological Rating Scale (CPRS) and depression and anxiety with Montgomery-Asberg Depression Rating Scale (MADRS) total scores than controls. Cases and controls did not differ regarding the total number of stressful events experienced. The uncontrollable events and undesiderable events had occurred more frequently among pemphigus patients than controls. In 68% of pemphigus patients at least one personality disorder was diagnosed; there was a high prevalence of obsessive-compulsive and avoidant personality disorder. These findings suggest that stressful life events might increase vulnerability to pemphigus and that personality features might modulate individual susceptibility to illness.