Although most patients with differentiated thyroid cancer (DTC) of follicular cell origin enjoy a relatively good prognosis, some patients unfortunately present with or develop locally advanced DTC which leads to significant local morbidity and mortality. DTC accounts for 54-94% of all locally advanced thyroid cancers. DTC invasion of the recurrent laryngeal nerve, strap muscles and trachea are the most common followed by invasion of the esophagus, internal jugular vein and carotid artery. Surgical resection is the primary treatment for locally advanced DTC. Although the optimal surgical approach (ranging from conservative shave excision to aggressive en bloc resection of tumor and vital structures) in patients with locally advanced DTC is controversial, a curative resection should be the goal unless complete tumor resection results in unwanted perioperative morbidity and mortality or widely metastatic disease is present. Postoperative radioiodine ablation with TSH suppression is imperative after surgical resection of locally advanced DTC. Patients with microscopic or small gross residual disease, after surgical resection, may benefit from postoperative external radiotherapy for local control of disease.