Mal de Meleda derives its name from its relatively high frequency among inhabitants of the Dalmatian Island of Mljet, Croatia, called Meleda in Italian, with 1 in 200 individuals affected. However, the condition has also been observed in countries distant from Mljet. In world populations, the disease has an average prevalence of 1 in 100,000. The disease was first described in 1826 and diagnostic criteria were presented in 1969. Mal de Meleda is a rare autosomal recessive disorder characterized by diffuse transgressive palmoplantar keratoderma, keratotic skin lesions, perioral erythema, brachydactyly, and nail abnormalities. Hyperkeratosis soon appears after birth and progresses with age and extends from the palms and soles onto the dorsal surface of the hands and feet, elbows and knees without involvement of other organs. A broad spectrum of clinical presentations has been described in patients with a diagnosis of Mal de Meleda. Histopathologically, hyperorthokeratosis and acanthosis, and foci of parakeratosis are also seen.