Tylosis, or focal epidermolytic palmoplantar keratoderma occurring after infancy, is associated with early-onset squamous cell carcinoma of the esophagus in three families. The tylosis is characterized by abnormal thickening of the palmoplantar skin. Neonatal onset of palmoplantar keratosis is a different disorder and not associated with esophageal cancer. The genetic locus for the tylosis esophageal cancer (TOC) gene has been localized to 17q25 (Langan et al. 2004) and the responsible gene has recently been identified.