The prognostic significance and the optimal management of regional lymph node metastases in patients with well-differentiated thyroid carcinoma continue to be controversial. The current surgical approach for nodal metastases is removal of grossly involved lymph nodes ("berry picking"). In patients with papillary thyroid cancer, this intraoperative sampling technique reveals tumor in only 15% to 60% of excised nodes. However, if a more extensive nodal dissection is undertaken, at least 70% of patients are found to have nodal disease. The authors have successfully used a gamma probe-guided lymph node dissection technique ("gamma picking") to identify visually undetectable micrometastatic lymph nodes at the time of surgical exploration. The authors used this technique in a 52-year-old man with papillary carcinoma of the thyroid that was diagnosed by fine-needle aspiration. Eighteen hours before the planned total thyroidectomy, the patient was given 1 mCi I-123 orally. Operative exploration revealed multiple tumor nodules in both lobes but no palpable lymph nodes in the neck. Total thyroidectomy was performed with complete extracapsular removal of both lobes and isthmus. The thyroid bed and the central and lateral nodal basins were scanned using a gamma probe (Neoprobe). Hot spots were identified, and these counts were compared with that of the background activity in the strap muscles. The gamma probe revealed four distinct foci of increased activity (10 times more than the background). These were resected and labeled separately for histopathologic study. Histologic analysis revealed bilateral, multifocal well-differentiated papillary carcinoma, with the largest tumor focus measuring 0.6 cm. Two of the four hot spots proved to be metastatic foci in small lymph nodes measuring less than 0.5 cm. The other two hot spots were thyroid remnants with no associated nodal tissue.