Abstract. Objective: The incidence of papillary thyroid cancer (PTC) is rising all over the world. The trace elements copper (Cu) and zinc (Zn) are essential for many physiological functions. Concurrent exposure to Cu and Zn may result in remarkable epithelial toxicity and stress. We evaluate the serum Cu and Zn concentrations as well as the Cu/Zn ratio to predict the possible malignancy of PTC in patients who underwent thyroid fine needle aspiration biopsy (FNAB) before total thyroidectomy. Material and methods: Serum Zn and Cu concentrations as well as the Cu/Zn ratio of 111 patients (23 male and 89 female) who underwent total thyroidectomy and in whom preoperative thyroid FNAB was non-diagnostic or demonstrated atypia of undetermined significance (AUS) or was suspicious for follicular neoplasm (SFN) or showed benignity were evaluated. Postoperative pathology results were classified as benign or malignant. The amount of Cu and Zn was determined using atomic absorption spectrometry. In the malignant group, preoperative serum Cu levels correlated with tumor size, localization, and focality. Results: In the malignant group, the preoperative Cu level and Cu/Zn ratio was found higher than in the benign group; also postoperative serum Cu difference and serum Cu/Zn difference showed a significant decrease when compared to the preoperative state (p = 0.001, 0.034, 0.002, 0.003, respectively). In receiver-operating characteristics (ROC) analysis, the optimal cut-off value of preoperative Cu for differentiating malignant tumor from benign tumor was found to be 158.88 mg/dL (p = 0.001; sensitivity: 48%, specificity: 84%). In subjects in whom FNAB results were non-diagnostic or revealed benignity, AUS, or SFN, preoperative Cu levels over 158.88 µg/dL to predict malignancy were found to have a sensitivity of 24%, 67%, 54%, and 50%, respectively, and a specificity of 70%, 82%, 93%, and 100%, respectively. Conclusions: Before thyroid surgery, if FNAB was non-diagnostic or revealed indeterminate cytology like AUS and SFN, the assessment of serum Cu is considered to be a useful diagnostic tool for surgical decisions in patients with thyroid nodules and for determining PTC cases.