Background: Oxidation products are assumed to play essential role in the pathogenesis of benign and malignant diseases of the thyroid. Objective: The aim of this prospective study is to examine advanced oxidation protein products (AOPP), lipid peroxidation product malonyldialdehyde (MDA), ferrous oxidation in xylenol orange (FOX) and the antioxidant enzyme activity of superoxide dismutase (SOD) in blood samples of multinodular goiter and papillary thyroid cancer patients before and after thyroidectomy and compare them to healthy controls. Methods: Thirty-seven papillary thyroid cancer and 43 benign multinodular goiter patients treated with total thyroidectomy and 35 healthy control subjects were included in this study. AOPP, FOX, MDA, and SOD levels were studied before and after thyroidectomy to determine oxidation products and antioxidant enzyme activities. Results: Before thyroidectomy, serum levels of AOPP, FOX, and MDA were significantly higher in both benign and malignant patient groups compared to control group (p<0.05). After thyroidectomy, serum levels of these markers were still higher in patients compared to the control subjects, however, their levels decreased in the malignant patient group (p<0.05). Serum level of SOD was higher only in benign thyroid disease group and decreased after thyroidectomy, but still was higher than malignant and control groups (p<0.05). Conclusions: In this pioneer study, although the number of patients were not sufficiently large to reach any clear conclusion, SOD serum levels may be promising in differentiating benign disease from malignant disease in thyroid patients and decreased SOD activity could be the essential pathogenesis of thyroid cancer.