Tumors of thyroid gland are one of the most prevalent forms of human cancers. Despite the various molecular mechanisms, mutations or polymorphisms of p53 have a potential role in the development and/or progression of human malignancies including thyroid. A common variation in p53 that results in adenine to proline change in codon 72 has been identified as a predisposing factor for various cancers since controversial results have been reported. In this study, we investigated codon 72 polymorphism in 58 Turkish thyroid cancer patients and 115 healthy individuals. Genomic DNAs were extracted from paraffin embedded tumor tissues of patients and blood samples of healthy individuals. PCR-RFLP method was applied for determination of codon 72 polymorphism. Genotype frequencies of arg/arg, arg/pro and pro/pro were 0.293, 0.483, 0.224 for patients and 0.461, 0.452, 0.087 for healthy controls, respectively. Proline allele frequencies of patients and healthy controls were 0. 466 and 0.313, respectively. A significant difference was found between genotypes of patients and controls (p=0.006). Also, proline allele frequency was significantly higher in patients group than healthy control (p=0.005) (Odds ratio=0.527, 95% CI= 0.341-0.817). No difference was found between 16 follicular adenoma and 18 papillary carcinoma patients (p>0.05). Additionally, no significant difference was found for TNM classification of papillary carcinoma patients for codon 72 status (p>0.05). In conclusion, p53 codon 72 polymorphism is a significant contributor of thyroid malign and benign lesions and proline allele is significantly increasing the risk of thyroid cancer.