Cytokeratins comprise a diverse group of intermediate filament proteins that are expressed as pairs in both keratinized and non-keratinized epithelial tissue. The cytokeratin proteins play a critical role in differentiation, as well as tissue specialization and function, to maintain the overall structural integrity of epithelial cells. Cytokeratins are also useful markers in identifying the origin of metastatic tumors. Cytokeratin 16 is expressed in benign stratified squamous epithelium and squamous cell carcinoma of the head and neck, as well as luminal cells of mammary gland and sweat ducts. It is absent in noninvasive breast carcinomas and normal breast tissue. Mutations in the Cytokeratin 16 gene cause various diseases, including pachyonychia congenita type 1 (PC1), nonepidermolytic palmoplantar keratoderma (NEPPK) and unilateral palmoplantar verrucous nevus (UPVN).