Background: Early recognition is crucial for successful treatment and good prognosis of oral cancer. A simple, noninvasive, and reasonably effective technique for initial evaluation of a suspicious oral lesion are exfoliative cytology. Micronuclei being structures presenting after genomic damage can be used as a screening tool in early detection of cancer. Method: A total of 60 subjects, 30 with potentially malignant disorders (PMD) (oral lichen planus and oral submucous fibrosis), 15 with oral squamous cell carcinoma (OSCC), and 15 with apparently normal mucosa, were included in the study. Cytological smears were collected from these groups and micronuclei were examined using Papanicolaou stain. One-way ANOVA was used to compare the mean micronuclei distribution among different study groups. Results: An increase in the frequency of micronuclei from normal to PMD to cancerous lesions was observed. Analysis has shown significant differences between various study groups (P < 0.05), with highest score observed in OSCC group, intermediary in PMD, and least in controls. Conclusion: The oral mucosal micronuclei can be used as a marker of epithelial carcinogenic progression.