Cytokeratins comprise a diverse group of intermediate filament proteins (IFPs) that are expressed in pairs in both keratinized and non-keratinized epithelial tissue, where they constitute up to 85% of mature keratinocytes in the vertebrate epidermis. Cytokeratins play a critical role in differentiation and tissue specialization and function to maintain the overall structural integrity of epithelial cells. The α-helical coiled-coil dimers associate laterally end-to-end to form 10 nm diameter filaments. Cytokeratins are useful markers of tissue differentiation, and in addition they aid in the characterization of malignant tumors. In Bowen’s disease, the characteristic malignancy of the epidermis exhibits distinct expression patterns of Cytokeratin 14. Mutations in the gene encoding human Cytokeratin 14 lead to epidermolysis bullosa simplex, an inheritied skin disorder characterized by skin blistering due to basal keratinocyte fragility.