Lymphatic mapping and sentinel lymph node biopsy (SLNB) have emerged as a promising minimally invasive surgical technique to detect metastatic nodes in patients with melanoma and breast, colon, esophageal, gastric, lung, head and neck, and thyroid cancers. The SLNB procedure is safe and feasible, with high accuracy in predicting occult metastases of differentiated thyroid cancer. The sensitivity of the SLNB technique has increased as technical details and complementary immunohistochemical and molecular techniques have been developed. SLNB for thyroid cancer may display practical benefits in accurate nodal staging, the detection of metastatic lymph nodes outside the central neck, and the selection of patients who would benefit from complete neck dissection and optimized (131)I ablation therapy. Currently, however, there is no direct evidence that SLNB is associated with long-term clinical and survival benefits in patients with thyroid cancer. Well-controlled prospective clinical trials will determine the clinical significance of occult metastases and their early detection by SLNB in patients with thyroid cancer.