This practical instruction course will describe an approach to improve pre-operative thyroid nodule diagnosis, management and prognostication through surgeon performed ultrasound, ultrasound guided fine needle biopsy and molecular testing. Risk stratification of a thyroid nodule based on ultrasound features will be detailed. Molecular alteration testing can help rule in and rule out cancer for thyroid nodules with indeterminate fine needle aspiration cytology. This practical overview will compare the Afirma Genomic Sequencing Classifier, Next Generation Sequencing, and ThyGenX + ThyraMIR as they point us toward an era of improved diagnostic capabilities and personalized medicine. The ATA guidelines for ultrasound and molecular testing will be interwoven.