Objectives: Oral cancer is a worldwide phenomenon. It is thought to develop in a number of premalignant lesions. Protooncogene c fos is a known transformer of premalignant to malignant lesions. However, its role in oral carcinogenesis is not yet known. Study design: A total of 130 cases were studied comprising of premalignant lesions (n=50), squamous cell carcinoma (n=50) and controls (n=30). c fos expression was studied by immunohistochemistry. Results: Premalignant lesions of oral cavity occurred at a lower age group (mean 39.2 years) compared to squamous cell carcinoma (mean 51.8 years), p <0.001. Mean c fos percentage positivity in squamous cell carcinomas (SCC), premalignant lesions and controls was 44.5±36.9%, 11.4±18.8% and 1.23±2.6% respectively, the differences were highly significant (p<0.001). c fos positivity also increased from mild (10.85±14.23%) to moderate dysplasia (19.64 ±26.05%). Conclusions: The serially increasing c fos expression from normal mucosa to premalignant lesions to SCC and in dysplasias suggests that it could be an early gene to get activated and form transcription factor activator protein ?1(AP-1).