Thyroid malignant nodules (TMNs) are the most common endocrine cancer and the fifth most frequently occurring type of malignancies. The etiology and pathogenesis of TMNs must be considered as multifactorial. The present study was performed to clarify the role of some chemical elements (ChEs) in the etiology of these thyroid disorders. Thyroid tissue levels of nineteen ChEs were prospectively evaluated in malignant tumor and tissue adjacent to tumor of 41 patients with TMNs. Measurements were performed using a combination of non-destructive and destructive methods: instrumental neutron activation analysis with high resolution spectrometry of short-lived radionuclides and inductively coupled plasma atomic emission spectrometry. Results of the study were additionally compared with previously obtained data for the same ChEs in “normal” thyroid tissue. It was observed that in malignant tissue the mass fractions of Al, B, Ca, Cl, Cu, K, Mg, Mn, Na, P, S, and Si were 3.14, 4.64, 1.79, 2.26, 3.55, 1.57, 1.61, 1.57, 1.24, 2.45, 1.14, and 2.81 times, respectively, higher whereas mass fraction of I was 25.6 times lower than in the normal thyroid. In the “adjacent” group mean mass fractions of Cl and I were approximately 1.6 and 1.7 times, respectively, higher, while mean values of Ba, Ca and Sr content were 55%, 45%, and 70%, respectively, lower than in the “normal” group. In tumor Ca, Cl, Cu, K, and Sr contents were approximately 2.8, 1.4, 1.8, 1.7, and 5.4 times, respectively, higher, while I content was 43 times lower than in “adjacent” group of tissue samples. It was concluded that thyroid tissue adjacent to malignant nodules kept the main function of thyroid gland, while malignantly transformed thyroid cells lost its capacity to accumulate I. It was supposed that the excessive accumulation of Cl and I by thyroid tissue probably precede the TMNs origination and development. It was also supposed that elevated levels of Al, B, Ca, Cl, Cu, K, Mg, Mn, Na, P, S, and Si, as well as drastically reduced level of me in cancerous tissue could possibly be explored for differential diagnosis of benign and malignant thyroid nodules.