Aim:Tobacco use is the major cause of oral cancer, which is the sixth most common form of malignancy globally. Even in the absence of clinical manifestations, early changes in the oral mucosa can be detected microscopically by exfoliative cytology. The present study aimed to study and compare the cellular changes in the oral mucosa of tobacco users using cytomorphometry.Materials and Methods:A total of 80 subjects were included: 20 without any tobacco use habits, 20 tobacco chewers, 20 smokers, and 20 mishri users. Smears were collected from each subject, fixed, and stained using Papanicolaou stain. All slides were evaluated for nuclear and cytoplasmic changes using image analysis software.Results:Statistically significant decrease in cytoplasmic area and an increase in nuclear area and nuclear-cytoplasmic ratio were observed in tobacco users.Conclusion:Tobacco in any form causes significant cellular changes, which could be the earliest indicators of developing malignant pathology. Exfoliative cytology can be used to detect such changes.