Abstract. Objective: Papillary thyroid carcinoma (PTC) is the most prevalent endocrine system malignancy with a fast-growing incidence in recent years. Due to the existing challenges in the diagnosis of thyroid lesions, improvement of specific molecular markers would be helpful to distinguish between malignant and benign thyroid tumors. In previous studies, trace element profile was investigated and reported as a potential marker for diagnosis of various cancers including thyroid cancer; however, some controversies exist as there is no consensus over the results of thyroid cancer studies. Therefore, this study was an effort to assess and compare the concentrations of some micro and trace elements in PTC as a malignant tumor, multinodular goiter (MNG) as a benign thyroid tumor, and healthy controls. Materials and methods: Serum micro and trace element concentrations (including Se, Cu, Zn, Mg, Fe, Mn, Ni, Ca, Ag, V, and the Cu/Zn ratio) from 18 PTC, 17 MNG, and 17 healthy subjects were compared using ICP-OES method followed by univariate and multivariate statistical analyses. Results: Multivariate methods showed that significant decrease of Cu/Zn ratio is the most important discriminating variable between malignant and benign thyroid lesions. Conclusion: The results confirmed that the trace element profile could serve as a helpful marker in differentiating malignant from benign thyroid tumors.