Objective: To clarify the association between the p53 polymorphism at codon 72 and susceptibility to thesporadic keratocystic odontogenic tumor (KCOT). Design: One hundred KCOTs and 160 match-group healthycontrols were genotyped to ascertain the frequency of the p53 codon 72 polymorphism using polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP), confirmed by direct sequencing. Results: Thefrequencies of the Pro/Pro, Arg/Pro, and Arg/Arg genotypes were 23.8%, 49.4%, and 26.9%, respectively, inthe controls, while the KCOT cohort demonstrated 43.0%, 39.0%, and 18.0%, respectively. Further analysissuggested that p53 Pro could be a KCOT-susceptible allele (OR (95%CI)=1.77 (1.22 to 2.59), p=0.0024), with asex-adjusted OR (95%CI) of 1.71 (1.17-2.50), p=0.0046. Moreover, the results indicated that p53 codon 72 Prohomozygous was associated with a two-fold risk of developing KCOT (adjusted OR (95%CI) =2.17(1.23-3.84),p=0.0062). Conclusions: The C/C genotype of P53 gene codon 72 increases the risk of developing sporadic KCOTand may be a useful tool for screening and diagnostic purposes.