In 2009, the Bethesda classification system for FNA reporting was introduced by the National Cancer Institute, and recently, revised, included six categories based upon cytopathological features, with an associated malignancy rate and standardized management recommendation for each category (Table 1) (10). FNA reliably establishes the diagnosis of a benign or malignant nodule in 70–80% of all cases (11) and has decreased the proportion of benign nodules unnecessarily resected from 86 to 50% (12). However, 20–30% of FNA cases have indeterminate or suspicious cytological results that include Bethesda III, IV, and V categories (12) and, of these, 6–75% are malignant on final surgical pathology (13, 14). Due to the uncertainty of malignancy in these patients, their management has been challenging, usually including a repeat FNA or a diagnostic lobectomy. For this reason, the need for distinguishing benign from malignant lesions in this subset of thyroid nodules has led to the pursuit of differentiating molecular markers.