Lymph node involvement appears to be the most significant prognostic factor in patients affected by melanoma and has been shown to reduce the five-year survival by 40%. We studied 31 patients (15 M; 16 F; age range, 28-83 years) with clinical stage 1 (CS1) intermediate thickness (0.75-4 mm) melanoma. Scintigraphic examination of the nodes was performed in all patients, 29 of whom underwent surgical biopsy of the SN after 24 hours. Early images were acquired 5, 15 and 79 min and late images 60-180 min following perilesional injection of 2-4 microdoses of 99mTc-nanocolloid (15-20 MBq). A cobalt marker was used to project the SN on the skin surface which was later stained with indelible ink. For intraoperative localization we used a portable probe and perilesional injection of patent blue violet dye, which proved positive in 24/29 patients (83%). After surgery histological examination of the sentinel lymph nodes (SNs) (hematoxylin-eosin and immunohistochemistry) found positivity for metastatic cells in 6 patients. They all underwent elective lymph node dissection (ELND); five are N0+ and are currently undergoing supportive therapy with interferon alpha with an 8-24-month follow-up, while one N+ patient died 14 months after surgery. Follow-up (3-26 months) of N0- patients has not evidenced any locoregional recurrence so far. Only one case showed hematogenic metastases. This procedure might radically change the therapeutic approach to CS1 melanoma because it is simple, scarcely invasive, and shows a favorable cost-benefit ratio.