The aim of our study was to provide a psychosocial and psychiatric evaluation of patients with epidermolysis bullosa (EB; a rare genetic disorder characterized by skin fragility), to assess psychological status, ascertain the presence of any psychiatric disorders and understand the impact of EB on quality of life. Twenty-five patients were assessed using a case record form and several standardized instruments. In 82% of patients, EB had a negative impact on quality of life and 80% of patients experienced psychiatric symptoms. Our findings revealed a high prevalence of psychosocial problems and psychiatric symptoms in patients with EB and suggested that a combined bio-psychosocial approach is the most appropriate therapeutic intervention.