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Cytokeratins are intermediate filament proteins expressed in cytoplasm of epithelial cells. The mitotically active basal layers of most stratified squamous epithelia express 10% to 30% of their total protein as keratin. The two keratins specifically expressed in these cells are the type II keratin CK5 and type I keratin CK14, which essentially form 8-nm filaments. CK5 and calretinin are useful immunohistochemical markers in different studies of mesothelioma, and their expression is key tool for the histological differential diagnosis with adenocarcinomas, especially when confronting with metastatic tumors of unknown origin. CK5 labels myoepithelial cells of breast and prostate basal cells. A combination of CK5, CK14 and p63, has been used as specific and sensitive cell marker of basal-like phenotype of breast carcinoma and to differentiate prostate cancer and normal cells. Loss-of- function mutations in the keratin 5 gene (KRT5) affected family members and in six unrelated patients with Dowling-Degos disease (DDD), an autosomal dominant genodermatosis. This indicates a crucial role for keratins in the organization of cell adhesion, melanosome uptake, organelle transport, and nuclear anchorage.