Cytokeratins comprise a diverse group of intermediate filament proteins (IFPs) that are expressed as pairs in both keratinized and non-keratinized epithelial tissue. Cytokeratins play a critical role in differentiation and tissue specialization and maintain the overall structural integrity of epithelial cells. Cytokeratins are useful markers of tissue differentiation which is directly applicable to the characterization of malignant tumors. Cytokeratin polypeptides are designated 1 to 20 and are divided into the type I and type II subgroups. The type II family members comprise the basic to neutral cytokeratins 1-8, while the type I group comprises the acidic cytokeratins 9-20. Cytokeratin 5 is expressed in normal basal cells. Mutations of the cytokeratin 5 gene (KRT5) have been shown to result in the autosomal dominant disorder epidermolysis bullosa (EB). Cytokeratin 6 is expressed in suprabasal keratinocytes of wounded epidermis and in acrosyringeal keratinocytes in normal skin. Cytokeratin 18 is one of the first keratins expressed in the embryo, and persists into adult tissues. It is a major component of all simple epithelia (but not of stratified squamous epithelia) and adenocarcinomas.