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Intermediate filament proteins (IFPs) are important markers of tissue differentiation and have been receiving increasing interest, in particular, through their applicability in the characterization of malignant tumors. Cytokeratins (Cks) are a family of IFPs that are typically specific for epithelial cells. They are expressed in certain combinations depending on the type of epithelium and the degree of differentiation. This review presents a critical analysis of the available data on Ck expression in normal and (pre) neoplastic epithelia of the head and neck region. Special attention is paid to technical and cell biologic pitfalls, which can lead to false-negative or false-positive data. It appears that only a limited fraction of the reported data contributes substantially to our knowledge of IFP expression in head and neck cancer because of the use of ill-defined, often formalin-fixed and paraffin-embedded, tissue specimens, and the application of limited panels of monoclonal antibodies. It is concluded that the use of immunocytohistochemistry is promising for the differential diagnosis of head and neck tumors and contributes to our knowledge on their biologic behavior. However, documentations of more complete Ck expression patterns of normal and (pre)malignant epithelium are required, together with their correlation to clinical parameters.