Background and Objective: The regular use of tobacco causes loss of cell cohesion, hyperkeratosis, and increased incidence of nuclear anomalies on the oral mucosa. Thus, the study was conducted to observe the impact of chewing tobacco on the nuclear changes in oral epithelial cells. Methodology: This was a prospective observational study conducted on 100 tobacco chewing subjects ranging from 20 to 70 years in age. The nuclear aberrations such as multi-nucleation, bi-nucleation, pyknosis, karyorrhexis, karyolysis, and condensed chromatin in Papanicolaou stained buccal smears. The t-test was applied to know the statistical significance. Results: The distribution of frequency of multi-nucleation, bi-nucleation, and condensed chromatin proved to be significantly higher. The overall results of pyknosis, karyolysis, karyorrhexis did not reach the level of significance. Conclusion: Microscopically examined nuclear changes are a useful tool in the early diagnosis of oral carcinoma.