<p>There has been remarkable growth in our understanding of the biologic behavior and molecular signature of thyroid malignancies, which has led to the introduction, application, and evolution of molecular testing of thyroid nodule FNA cytology. Next-generation sequencing molecular testing is an important, well-validated diagnostic tool for management of cytologically indeterminate thyroid nodules. It reduces unnecessary thyroid surgery for benign disease, avoiding associated surgical risks for the patient and reducing healthcare expenses. This article reviews the development and implementation of thyroid nodule cytologic classification and subsequent testing and how it has improved the diagnostic considerations in thyroid nodule and thyroid cancer management algorithms. The use of molecular testing as a prognostic tool is evolving and although the data are limited, they suggest a promising role in prognostication for oncologic outcomes. However, future studies are needed to further evaluate this.</p>