Thyroid nodules are very common in the adult population, but only a minority of them harbor a malignant lesion. Therefore, the first aim in their clinical evaluation is to exclude malignancy. To date, the fine-needle aspiration cytology (FNAC) represents the main diagnostic tool for the evaluation of thyroid nodules and cervical lymph nodes (CLN) suspected of metastatic disease. It has to be mentioned, however, that FNAC on thyroid nodules suffers from a major diagnostic limit represented by cellular atypias of indeterminate significance, which require the histological diagnosis. Also the FNAC performed on CLN may be a challenging diagnostic category as CLN could harbor metastases from a multiplicity of extrathyroidal malignancies or be affected by several non-tumoral diseases. In addition, inadequate cellularity obtained from both thyroid nodules or CLN prevents diagnosis in about 20% of specimens. Total thyroidectomy followed by adjuvant therapy with 131I is the treatment of choice for most patients affected by DTC. Although the prognosis of DTC patients is favorable, about 20% of them face the morbidity of disease recurrence and tumor-related deaths. Thus far, the prognosis of these patients still relies on clinic-pathological variables such as patient’s age, tumor size, histology, lymph node or distant metastasis, which are not accurate in predicting the long-term outcome. As a consequence, the identification of new molecular biomarkers strictly related to the risk of DTC relapse is highly needed. In the present review we’ll attempt to summarize the recent characterization of new molecular markers able to ameliorate the diagnosis and prognosis of thyroid cancer patients.