Background: Oral cancer is creating an alarming situation globally. It is the commonest cancer in India, accounting for 50__ampersandsignndash;70% of total cancer mortality. Oral cancer is amenable to primary and secondary prevention. The relationship between ABO blood groups and carcinogenesis or progression of human tumors has been reported by many investigators. Aim: To evaluate the association of ABO Blood Group System with Potentially Malignant Oral Lesions and Oral Cancer and also assess other risk factors associated with age, sex and tobacco habit. Material and Method: The research was a case-control study including 200 subjects selected using the random sampling technique into 4 groups, two control and two experimental 100 each. Details regarding demographics and oral habits were noted followed by blood group testing and comparison of blood groups and Rh status of all 4 groups. For statistical analysis, a Chi-square test was used to assess the relationship between ABO blood groups and oral precancer and cancer. The probability level was fixed at __ampersandsignle;0.05. Results: A significant association between the blood group A and the defined diseases could be determined. Common age group for Oral cancer was found to be 51-60 years with male preponderance. Oral Submucous Fibrosis was the most prevalent precancerous disorder with smokeless tobacco being the chief etiological factor. Conclusion: ABO blood group may have a role in the causation of oral precancer and cancer, and this novel finding provides a hint that ABO blood group may be used as a possible indicator although we cannot rule out the presence of residual confounding by other predisposing factors for oral cancer. Nonetheless, further investigations that include more diverse study populations are warranted.