Mal de Meleda (MDM) is a rare sub-type of palmoplantar keratoderma (PPK) disease. The primary symptoms of PPK are scleroatrophy, transient keratoderma, scleroatrophic erythema, pseudoainhum around the digits, and perioral erythema. MDM is a pathology with a difficult clinical course. This case study presents two cases of MDM in siblings born out of second-degree consanguinity. The presenting complaint was the peeling of the palmar skin since birth. Both patients were treated with acitretin orally (dose: 10 mg) for three months and tretinoin (topical) for two months. The prognosis was good after three months of treatment.