A 40-year-old manatee was referred with recurrent vesicular and ulcerative dermatosis for the past 15 years. During this period the animal was anorectic and lost weight. Differential diagnoses were formulated on the basis of the history and clinical signs. Skin scrapings, bacterial and fungal culture, cytological examination, blood examination, and histopathological examination of skin biopsies narrowed this list down to autoimmune dermatosis. Despite corticosteroid therapy the symptoms recurred and the animal died. Histopathological examination of post-mortem skin biopsies showed again autoimmune dermatosis, more specifically subepidermal bullous autoimmune dermatosis, as the most probable cause of the skin lesions. Post-mortem examination showed cardiac decompensation and chronic nephritis. It was impossible to estimate the possible contribution of the chronic dermatosis to the cause of death. The purpose of this case report is to show the importance of a systematic work-up of disease in exotic animals.