The finding that the presence of micrometastases in the first draining primary (sentinel) lymph node potentially reflects the incidence of regional micrometastases has created a fundamental change in how a node-negative lymphatic basin can be evaluated and managed. In cutaneous melanoma and carcinoma of the breast, the data verify the significance of the primary lymph node and support the importance of primary lymph node biopsy. Gamma-probe localization and biopsy of the primary node is a safe, minimally invasive technique that is accurate and easy to perform. For many patients, this technique permits the surgical staging of the regional lymphatics to be performed under local anesthesia on an outpatient basis. Our experience with squamous cell carcinoma of the head and neck and Merkel cell carcinoma suggests that the assessment of the regional lymphatics using the gamma-probe technology for identification of the primary node may also be applicable to many other solid tumors.