Historically, clinicopathologic risk assessment of thyroid cancer (TC) has often been inaccurate, and the overtreatment of inherently low-risk TC and under-treatment of potentially aggressive TC commonplace. However, our knowledge of the molecular makeup of TC, and the genetic determinants of tumorigenesis and progression, has grown considerably over the past decade. This has heralded in a new era of molecular-based risk stratification, based upon the presence/absence of informative cancer mutations, which can more precisely guide clinical management. To date, the most extensively validated TC biomarker is BRAFV600E, which while never being present in benign disease, is detected in about two-thirds of all TC. BRAFV600E is associated with more aggressive disease and is clearly associated with locoregional recurrence, but not with distant metastases or death independently from other clinicopathological risk factors (1-2). More recently, TERT promoter mutations (TPMs) have also be shown of predictive value, occurring with increasing frequency in progressively worsening prognostic TC subtypes (3); and within relatively indolent differentiated TCs, to be correlated with adverse prognostic features such as older age, larger tumour size and male gender (4) Furthermore, several studies have found an interaction between the presence of TPMs and BRAFV600E in predicting recurrence (4). This talk will provide current overview of these and other promising biomarkers, where the field is currently, and the exciting developments that are on the horizon; including novel approaches beyond tumor DNA sequencing, such as transcriptomics, epigenomics and immunophenotyping. We will also review current and potential applications of liquid biopsy-based biomarkers, such as circulating tumor cells and circulating nucleic acids, a new modality which is transforming oncology.