Objective to investigate the expression of Ki-67, phosphohistone H-3 (PHH3), and cytokeratin 15 (CK15) proteins in the cells of the oral mucosa (OM) according to the degree of its malignant transformation. Material and methods. OM biopsy specimens from 69 patients diagnosed with focal epithelial hyperplasia, intraepithelial squamous cell neoplasia, cancer in situ, and squamous cell carcinoma were examined. Tissue antigens were determined using mouse Ki-67 monoclonal antibodies, rabbit PHH3 polyclonal antibodies, and mouse CK15 monoclonal antibodies. Results. There was an increase in epithelial proliferative and mitotic activities in squamous cell carcinoma and a sharp decrease in the expression of CK15 in the cytoplasm in cancer in situ and squamous cell carcinoma of the OM. Conclusion. The protein CK15 can be used for the differential diagnosis between high-grade dysplasia and OM epithelial malignancy at the stage of carcinoma in situ and squamous cell carcinoma. © A.A. IVINA, V.A. SEMKIN, Z.S. KHABADZE, I.I. BABICHENKO.