Abstract: Darier's Disease is an autosomal dominant genodermatosis characterized by an abnormality in keratinization. The typical lesions are warty papules with a dirty aspect, that may fuse and form vegetating malodorous plaques, particularly in intertriginous areas, beginning generally in childhood. Affects nails and mucosa also. Generally begins in childhood, worsening throughout the years, affecting life quality. Different treatments have been proposed depending on the extension and severity of the disease. For the severe forms of the disease systemic retinoids, isotretinoin or acitretin and formely etretinate, are the drugs of choice. The introduction of retinoids either continuously or intermittently give relief of symptoms, particularly the pruritus and an almost complete remission of the warty lesions. The vegetating plaques of intertiginous areas are more resistant to therapy, requiring additional local care. We report the case of a 69 year-old white male, born by a complicated vaginal delivery, resulting in neurologic damage with consequent moderate mental retardation and onset of seizures at the age of 53 year-old, treated with phenobarbital. Darier's Disease was diagnosed at the age of 19 year-old with a severe involvement of almost all the entire skin surface, with vegetating plaques in the groins and papillomatous lesions on the ears. With 49 year-old he received etretinate for nine consecutive years at a dosage of 50 mg/day. It was withdrawed on account of an untreatable diarrhea, attributed to the drug. Three years later we reintroduced another systemic retinoid, acitretin, available in the Health Department of the State. We used it at a dosage of 30mg/day with a very impressive improvement of the cutaneous lesions, except for those of the groins. Even the papillomatous lesions of the ear disappeared. The only side effects of the drug was a moderate increase in total cholesterol (237 mg/dl) and triglycerides (270 mg/dl). The phenobarbital was recently changed to clonazepam and both drugs were used with acitretin without adverse interaction between them. The introduction of acitretin had an important impact on the patient life quality, particularly because the malodorous lesions remitted.