Background and Purpose: The investigators designed and implemented a prospective cohort study composed of smoking and nonsmoking patients with asymptomatic fully impacted mandibular third molars. The objective of the paper was to evaluate 21 single-nucleotide polymorphisms (SNP) on the TP53 gene in smokers' (S) and nonsmokers' (NS) pericoronal follicles of asymptomatic impacted third molars. Materials and Methods: Matrix-assisted desorption/ionization time of the flight mass spectrometry was used for SNP analysis of 21 regions in the TP53 gene. Descriptive statistics and Chi-square tests were computed with a P value of 0.05. Results: Ten of the 21 SNPs related to oral pathologies according to NCBI dbSNP, were detected; in these, the genotypic frequencies showed no differences between the S and NS groups (P > 0.05). The results showed a high ratio of SNPs without correlation between smoking and TP53 gene status. Conclusion: Further studies should examine the entire TP53 gene to elucidate how smoking affects it in larger study populations.