Congenital symmetrical interdigital hyperkeratosis is a rare disorder described by Frei in 1923, characterized by localized hyperkeratosis of the interdigital spaces of the hands and feet. The authors report the case of a 7-year-old girl affected by this condition. The skin hyperkeratotic lesions appeared localized exclusively to the interdigital spaces of the hands. Histologic examination showed orthokeratotic hyperkeratosis, hypergranulosis and acanthosis. Keratolytics failed to improve the clinical picture.