Thyroid cancer is the most common endocrine malignancy with an estimated 43,800 new cases to be diagnosed in 2022 and representing the 7th most common cancer in women. While thyroid nodules are very common, being identified in over 60% of randomly selected adults, only 5-15% of thyroid nodules harbor thyroid malignancy. Therefore, it is incumbent upon physicians to detect and treat thyroid malignancies as is clinically appropriate and avoid unnecessary invasive procedures in patients with benign asymptomatic lesions. Over the last 15-20 years, rapid advances have been made in cytomolecular testing to aid in thyroid nodule management. Initially, indeterminate thyroid nodules, those with Bethesda III or IV cytology and approximately a 10-40% risk of malignancy, were studied to assess benignity or malignancy. More recently, next generation sequencing and micro-RNA technology platforms have refined the diagnostic capacity of thyroid nodule molecular testing and have introduced opportunities to glean prognostic information from both cytologically indeterminate and malignant thyroid nodules. Therefore, clinicians can move beyond determination of malignancy, and utilize contemporary molecular information to aid in decisions such as extent of surgery and post-therapy monitoring plans. Future opportunities include molecularly derived information about tumor behavior, neo-adjuvant treatment opportunities and response to thyroid cancer therapies.