In 1901, Vorner described a diffuse keratoderma of palms and soles with autosomal dominant inheritance. Histopathologically, this disease has the typical features of epidermolytic hyperkeratosis. Clinical examination does not allow differentiation between keratoderma of the Vorner type and the keratoderma described by Thost in 1880 and Unna in 1883. Reexamination of the family originally seen by Thost revealed histopathological signs of epidermolytic hyperkeratosis, confirming that keratoderma of the Vorner type is present in this family. The clinical features and variability of this palmoplantar keratoderma were demonstrated on the basis of an examination of 22 families (46 patients). In addition to diffuse hyperkeratosis of palms and soles with a sharp demarcation and erythematous margin, some less well-known features, such as knuckle pad-like keratoses on the finger joints and clubbing of the nails were observed. A genetic analysis of the pedigrees suggests that new mutations causing this disorder rarely occur. Point mutations in the keratin 9 gene, which has been mapped to chromosome 17q21, can be a cause of epidermolytic keratoderma of palms and soles. Five different keratin 9 gene mutations were identified. All these mutations are localized in the highly conserved coil 1A region of the rod domain, which is thought to be relevant for dimer formation in intermediate filaments.