Introduction. Oral verrucous carcinoma is classified as a well-differentiated squamous cell carcinoma. Histologically, it is characterized by hyperkeratosis, epithelial hyperplasia, preservation of basal membrane integrity, and chronic inflammation in the lamina propria of the mucosa. The development of ver rucous carcinoma typically begins with verrucous hyperplasia, which exhibits a histological pattern similar to that of verrucous carcinoma. For a more accurate diagnosis, immunohistochemical methods are used. The proliferative activity of cells is assessed using the Ki-67 marker. Alterations in tumor cell apoptosis are studied by examining the p53 protein in its two forms: wild-type (WTp53) and mutant-type (MTp53). The paper aimed to evaluate immunoreactive cells for Ki-67 and p53 proteins in verrucous hyperplasia and verrucous carcinoma. Materials and methods. To investigate verrucous hyperplasia and verrucous carcinoma, we examined oral mucosal biopsy samples obtained from patients with a preliminary clinical diagnosis of leukoplakia. A total of 27 cases were analyzed, including 18 cases of verrucous hyperplasia (66.6%) and 9 cases of verrucous carcinoma (33.3%). Proliferative activity was assessed using anti-Ki-67 antibodies. For p53 analysis, two antibody clones were used: DO-7, which detects both wild-and mutant-type proteins, and Y5, which specifically detects the mutant form. Results. Immunoreactive cells for WTp53 protein accounted for 19.4% (16.40; 21.10) in verrucous hyperplasia compared to 26.0% (25.70; 27.10) in verrucous carcinoma, with higher nuclear staining intensity observed in the latter. For MTp53 protein, the values were 5.1% (2.90; 5.60) in verrucous hyperplasia and 28.1% (27.10; 29.90) in verrucous carcinoma. The presence of isolated immunopositive cells in the verrucous hyperplasia group may be interpreted as early genomic alterations and the onset of neoplasia. Conclusion. MTp53 protein can be used for the differential diagnosis of verrucous hyperplasia and verrucous carcinoma, as the presence of immunopositive cells indicates genomic mutations in oral mucosal epithelial cells. © 2025 Elsevier B.V., All rights reserved.