Transforming growth factor, beta receptor II (70/80 kDa) (TGFBR2) is a tumor suppressor. Mutations in the TGFBR2 gene appear to have an increased risk of developing several cancers. To investigate whether TGFBR2 polymorphisms are associated with the development of papillary thyroid carcinoma (PTC), three single nucleotide polymorphisms (SNPs) of TGFBR2 (rs764522, -1444C/G; rs3087465, -834G/A; rs2228048, Asn389Asn) were selected and genotyped by direct sequencing in 92 PTC patients and 330 control subjects. We also assessed the relationships between three SNPs of TGFBR2 and clinicopathologic characteristics of PTC such as size (<1cm and ${geq}1cm$), number (unifocality and multifocality), location (one lobe and both lobe), extrathyroidal invasion, and lymph node metastasis. SNPStats and Haploview version 4.2 were used to analyze genetic data. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, overdominant, and log-additive) were performed to calculate odds ratios (ORs), 95% confidence intervals (CIs), and P values. The three examined SNPs were not associated with PTC. In clinicopathologic characteristics, two promoter SNPs (rs3087465 and rs764522) were associated with lymph node metastasis (rs3087465, P=0.009 in the codominant1 model, P=0.043 in the dominant model, P=0.003 in the overdominant model; rs764522, P=0.021 in the codominant1 model, P=0.044 in the dominant model, P=0.016 in the overdominant model). The synonymous SNP rs2228048 was associated with extrathyroidal invasion (P=0.024 in the dominant model, P=0.015 in the log-additive model). The allele frequency of rs2228048 was significantly different between PTC with extrathyroidal invasion and PTC without extrathyroidal invasion (P=0.018, OR=0.46, 95% CI=0.24-0.88). These results suggest that TGFBR2 may be associated with the progression of PTC in Korean population.