Background: An association between restriction fragment length polymorphism (RFLP) of known oncogenes and a predisposition to develop cancer has been postulated. Our aim was to test the hypothesis that there was an association between the L-MYC S allele in oral squamous cell carcinoma (OSCC) and a predisposition for the disease. Patients and Methods: The distribution of L-MYC polymorphism in 80 patients with OSCC was determined by polymerase chain reaction-based RFLP and compared with that of 60 healthy controls. Results: There was no significant difference between patients with OSCC and healthy controls. Patients with the L-MYC S allele and a positive family history of cancer were found to be 1.74 times more at risk for OSCC than those with any other genotype (95% confidence interval=0.88-3.45). Moreover, tumor recurrence was higher among individuals carrying a L-MYC S allele than those with any other allele type. Conclusion: L-MYC polymorphism was not a significant marker for predicting susceptibility to OSCC in this population but may, be a useful marker for identifying patient susceptibility to tumor recurrence and to developing OSCC, especially in individuals having a family history of cancer.