Thyroid cancer is the most common endocrine malignancy and among the major types, papillary thyroid carcinoma (PTC) represents 90% of all thyroid carcinomas. Several studies have identified in PTC recurrent somatic genetic alterations in known oncogenes (i.e., BRAF, RAS and RET). Recently, hTERT promoter mutations have been observed in approximately 11% of PTC with aggressive behavior, and together with other genetic mutations, like TP53 mutations, have been associated with aggressive forms of PTC. Cancer cells show profound metabolic alterations and a perturbed redox homeostasis, allowing them to meet the metabolic and biosynthetic needs. Redox state, which, together with altered metabolism, is considered a hallmark of cancer cells, is closely dependent on various metabolic pathways, resulting in a crosstalk between metabolism and redox homeostasis. Currently, cancer research and the evaluation of targetable features, have met a new challenge, due to the heterogeinity of tumor and the different cell populations behaviour whitin the tumor mass. Indeed, PTCs, as most tumors, are constituted by a subset of cells, cancer stem cells (CSCs), which are crucially involved in tumor progression and recurrence more than the differentiated tumor cells. CSCs exhibit a distinct metabolic phenotype, supporting tumor growth and survival, but how they adapt their metabolism to the cancer process is still unclear, and no data are yet available for PTC. Understanding this metabolic remodeling and dependence is essential to elucidate the fundamental mechanisms of tumorigenesis as well as to find new therapeutic strategies, targeting cancer metabolism. Among all the possible anti-tumoral compounds, high-dose of vitamin C has been showed to exhibit cytotoxic effect in cancer cells, primarily mediated by pro-oxidant and metabolic effects. However, the exact role of vitamin C in the metabolic perturbation and its potential use as a therapy target in cancer treatment and prevention in PTC in still poorly understood and require further ...