The paper presents an example of an immunohistochemical study of malignancy in oral epithelial hyperplasia. In the described case in view of the difficulty in determining the onset of the epithelial malignancy with the usual histological technique, an immunohistochemical method was used with antibodies to proteins Ki-67, human papillomavirus (HPV) type 16 and cytokeratin 15. The results of immunohistochemical study indicated increased proliferative activity of epithelial cells, presence of papillomavirus HPV16 in their cytoplasm and synthesis of cytokeratin 15 in all layers of the epithelium. These characteristics of squamous intraepithelial neoplasia may be a diagnostic criterion for the beginning of oral epithelial malignization.