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Renal cell carcinoma (RCC) represents 3% of human malignant tumors and approximately 90% of malignant renal neoplasms. Despite great therapeutic advances in the last decade, metastatic RCC (mRCC) is still considered an incurable disease. In this study, we examined the potential of essential elements as biomarkers of mRCC using an orthotropic metastatic mouse model. Frozen lung and plasma samples from healthy and mRCC-induced mice were lyophilized, digested, and analyzed using inductively coupled plasma mass spectrometry. In metastatic lungs, a significant increase in Ca concentration (268%) was observed, whereas a significant decrease in Cu (23.2%), Fe (17.4%), Mn (38.8%), and Na (11.7%) was observed. The plasma of mRCC-induced mice showed decreased concentrations of Mn (53%), Na (19.7%) and Zn (49,50%) and increased levels of Ca (53%), Cu (39.5%), Our findings revealed marked differences in the concentrations of essential elements in the lung and plasma of the metastatic mouse model. The circulating levels of Ca, Cu, Mn, Na, and Zn could be utilized as diagnostic and therapeutic response biomarkers.