Introduction: Betel quid (BQ) chewing is widely prevalent in India and many parts of Asia. The International Agency for Research on Cancer (IARC) has listed BQ as group 1 human carcinogen, related with multistage progression in oral squamous cell carcinoma (OSCC). Areca nuts, Catechu, Slaked lime with betel leaf are major components of Betel quid. Nitrosamines formed from alkaloids in betel nut may be implicated in the etiology of oral cancer. OSCC are characterized by complex karyotype that involves many chromosomal aberrations (CA). The CYPs families are involved in the metabolic activation of BQ and also areca nut-specific nitrosamines. Human CYP2A subfamily members play important roles in the metabolic activation of areca nut alkaloids, which is one of major causes of OSCC. CYPs are located on human chromosome19. Methods: In this study cases were screened from Department of E.N.T. & Oral and Maxillofacial surgery of RKMSP Hospital, ESI Hospital, Sealdah, Kolkata and different parts of Eastern and North Eastern states of India. Blood leukocyte cultures were analyzed for mitotic index (MI). CYP2A6 gene polymorphism was studied from EDTA blood. Results: Mitotic index are higher in cancer and pre cancer cases with chromosomal aberration (CA) than normal. Early metabolizers (EM) are susceptible to oral cancer but in case of poor metabolizers (PM) chances are less. Poor metabolizers (PM) are less prone to oral cancer due to CYP2A6 gene polymorphism. Conclusion: Prolonged habit of betel quid and its ingredients (which act as a mood elevating food in the world) are related with oral cancer.