: Gene expression for the differentiation‐specific keratins (K4, K13, K1 and K10) was analyzed in oral non‐dysplastic keratoses, oral lichen planus (OLP) and lichenoid reactions (LR) by comparative in situ hybridization (ISH) and immunohistochemistry (IHC) to investigate molecular changes in the altered differentiation pattern from non‐ to para‐ or orthokeratinization. At the protein level, K4 and K13 were detected homogeneously in the suprabasal compartment of parakeratotic epithelium but showed reduced expression in orthokeratoses, particularly in the presence of lymphocytes. Corresponding transcripts were restricted to basal and lower prickle cells. Synthesis of K1 and K10 was upregulated and more pronounced in orthokeratotic epithelia. The study showed an alteration in the pattern of differentiation‐specific keratins, although involvement of the lymphocytic infiltrate in OLP and LR resulted in further gene modulation. In both diseases, K1 and K10 showed transcriptional control, proteins having the same distribution as their transcripts. This represented a change from post‐transcriptional regulation in normal buccal epithelium, in which mRNAs for K1 and K10 are more widely expressed than their proteins. Thus, the pattern of keratin gene expression may be altered in response to frictional/smoking stimuli or immune‐mediated mechanisms.