Patterns of cytokeratin expression in squamous cell carcinomas of the tongue were examined by two-dimensional gel electrophoresis of cytoskeletal proteins and by immunofluorescence microscopy using antibodies specific for certain cytokeratins. The results were compared with those obtained from normal tongue mucosa. All carcinomas examined synthesized large amounts of cytokeratins as well as of desmosomal proteins such as desmoplakin(s) but differed from the normal tissue by the specific cytokeratin pattern expressed and by their heterogeneity of expression, which in immunofluorescence microscopy resulted in patchy, staining patterns. In general, the carcinomas showed a reduction of the amount of certain cytokeratins such as Nos. 4 and 13 which are abundant in normal epithelium. On the other hand, some other cytokeratins were present in relatively increased proportions, and certain subtypes of lingual carcinomas revealed, in addition, significant levels of cytokeratins 8 and 19 which are commonly considered to be typical of simple epithelial cells and tumours derived therefrom. To explain the differences of cytokeratin patterns between these tumours and normal epithelium as well as between different forms of squamous cell carcinomas two hypotheses are discussed, i.e. clonal selection of certain cells present in the original epithelium, probably in the basal layer(s), and different pathways of differentiation in the cell progeny derived from the transformed cell(s) of origin. The heterogeneity of cytoskeletal protein patterns in different lingual carcinomas, which was also noted for oropharyngeal, hypopharyngeal and laryngeal carcinomas, is discussed in relation to different kinds of response to therapeutical treatment.