Mal de Meleda (MDM), also known as keratodermapalmoplantaris transgrediens, is a rare inherited form of palmoplantar keratoderma. This condition is characterized by diffuse erythema and hyperkeratosis of the hands and feet that appears soon after birth and progressively extends to the dorsal aspect of the hands and feet. Treatment options for MDM include topical keratolytic agents, propylene glycol, topical 5-fluorouracil and surgical treatment. In addition, it has been reported that etretinate and acitretin, which are aromatic retinoids, usually produce improvement in MDM, although a successful response is not always seen. A 20-year old woman, previously diagnosed as MDM by gene mutation in SLURP-1, had administered oral acitretin 20 mg/day for 30 months, but the clinical features did not show the significant change. After 3 months of treatment with alitretinoin 30 mg/day instead of acitretin, however, her symptoms and signs improved significantly. Especially, the extent and thickness of palmoplantar hyperkeratosis decreased significantly. No local or systemic adverse events were observed. Herein, we present a case of MDM which showed significant clinical improvement with alitretinoin, which could be a new and promising treatment option for MDM.