Risk stratification is essential in the preoperative evaluation and management of thyroid nodules, most of which are benign. Advances in DNA and RNA sequencing have shed light on the molecular drivers of thyroid cancer. Molecular testing of cytologically indeterminate nodules has helped refine risk stratification, triage patients for surgery, and determine the extent of surgery. Molecular platforms with high negative predictive values can help identify nodules that may be spared surgery and can be managed conservatively. Here we discuss the importance of integrating cytomorphologic, molecular, and histologic features to help avoid errors and improve patient management.