Cytokeratin 4 (CK4) is a 59 kDa intermediate filament protein associated with Cytokeratin 13. It is expressed in suprabasal cells of non-keratinized stratified squamous epithelium of esophagus, cornea, anus, larynx, pharynx and tongue. A mutation in CK4 gene causes white sponge nevus. A decreased expression of CK4 is associated with head and neck squamous carcinoma. It is helpful in differentiation of squamous cell carcinoma of esophagus origin from thyroid origin.