Background: Recent reports indicated that incidence of thyroid carcinoma is increasing throughout the worldwide. The aim of our study was to determine a possible relationship between Forkhead box El (FOXE1) gene variants and histopathological features of papillary thyroid carcinoma. Methods: FOXE1 gene variations; rs894673, rs1867277 and rs3758249 were analyzed in 57 Papillary thyroid carcinoma patients and 51 age matched healthy control subjects. Restriction fragment length polymorphism (RFLP) technique was used to specifically detect the variations. Results: There was a significant difference in the distribution of rs894673 genotypes in Papillary thyroid carcinoma cases (P=0.01). AA genotype presence of rs1867277 was more significantly associated with several histopathological parameters such as focal and diffuse capsular invasion, lymphatic invasion, P3 with P4 tumor grade and surgical margins. AA genotype presence in rs1867277 variation was significantly associated with the classical variant which is subtype of papillary thyroid carcinoma. Furthermore, the presence of the allel A was found to be related with lymph node invasion risk by 2.46 fold, capsular invasion risk by 2.97 fold, and pT3 with pT4 pathological stage risk by 4.13 fold and the presence of allele A in rs1867277 was significantly associated with classic variants. The presence of allele A in rs1867277 was more significantly associated with several histopathological parameters in classic variant in papillary thyroid carcinoma cases such as, the presence of the A allele was found relationship with lymph node invasion risk by 2.0 fold, capsular invasion risk by 2.39 fold, and pT3 with pT4 pathological stage risk by 3.57 fold. In addition, AATT, AAAA and GATT haplotypes (rs1867277 and rs894673) were evaluated for association with papillary thyroid carcinoma cases. Our results indicate that the significant difference according to two-allele haplotype distribution between papillary thyroid carcinoma cases and control groups. Conclusion: Our findings suggest that FOXE1 variations generate a higher risk for poor histopatological features of papillary thyroid carcinoma.