Despite the extensive research, molecular markers for separating benign and malignant neoplasms or identification of the subgroup of patients with papillary thyroid carcinoma (PTC) and higher risk for more aggressive biological behaviour are yet to be found. The connection of Piwil2 and HMGA2 overexpression, either proteins or genes, with more aggressive clinical course was identified in several malignant neoplasms. Recent studies were focused on separating benign and malignant thyroid tumors. The correlation between piwil2 and HMGA2 overexpression and clinical progression of PTC has not been investgated. The aim of this research was immunohistochemical analysis of piwil2 and HMGA2 expression in PTC with and without regional lymph node metastasis (RLNM) as well as in follicular adenomas (FA), hyperplastic nodules (HN) and non-neoplastic thyroid tissue (NNTT). By retrospective analysis of 150 tissue samples (30 PTC with RLNM and 30 PTC without RLNM, 30 FA, 30 HN, 30 NNTT) it was determined that expression of piwil2 i HMGA2 was significantly higher in PTC (96,7%, 96,7%) as opposed to FA (73,3%, 13,3%), HN (63,3%, 3,3%) and NNTT (76,7%, 0%), respecively, (P<0,001). There was no statistically significant difference in expression of piwil2 and HMGA2 between PTC with RLNM and PTC without RLNM (100,0% vs 96,7%; 93,0% vs 96,7%, respectively). Overexpression of piwil2 and HMGA2 can not be associated with more aggressive biological behaviour of PTC. HMGA2 overexpression predicts PTC with high sensitiyity (97,78%) and specificity (100%).