Eighty-eight consecutive patients (48 men and 40 women; mean age, 58.9 years; range, 16-84 years) with clinically localized cutaneous melanoma involving the trunk, extremities or head and neck underwent lymphatic mapping at our institution. The primary melanoma had a mean thickness of 2.74 mm (range, 0.95 to 9 mm). Patients were divided into two groups: group A (39 patients) underwent only vital blue dye (VBD) mapping, while group B (49 patients) underwent lymphatic mapping with VBD and radio-guided surgery (RGS) combined. In all patients 1-1.5 mL of VBD was injected subdermally around the biopsy scar 10-20 min before surgery. In group B 37 MBq in 150 microL of 99mTc-HSA nanocolloid was additionally injected intradermally 18 h before surgery (3-6 aliquots injected perilesionally). In all lymphatic basins where drainage was noted the sentinel lymph nodes (SNs) were identified and marked with a cutaneous marker. Final identification of the SN was then performed externally by a hand-held gamma probe. After the induction of anesthesia 0.5-1-0 mL of patent blue V dye was injected intradermally with a 25-gauge needle around the site of the primary melanoma. SNs were examined by routine hematoxylin and eosin (H&E) staining and immunohistochemistry. Patients with histologically positive SN(s) underwent standard lymph node dissection (SLND) in the involved lymph node basin. The SN was identified in 37/39 patients (94.9%) of group A and in 48/49 patients (98.0%) of group B. Blue dye mapping failed to identify the SN in 5 of the 88 patients (5.8%), while the radioisotope method failed in only 1 of 49 patients (2.0%). Similar results were obtained with the combined use of the two probes. The average number of SNs harvested was 1.9 per basin sampled, which does not differ significantly from the numbers reported by other authors. The SN was histologically positive in 18 patients (20.5%). None of the 12 patients with a Breslow thickness less than 1.5 mm had positive SNs, whereas 18 of the 77 patients (23.4%) with a Breslow index exceeding 1.5 mm showed metastatic SNs with H&E or immunohistochemistry. The latter all underwent SLND of the affected basin. In 10 patients (55.6%) the SN was the only site of tumor invasion; eight patients (44.4%) with positive SNs had one or more metastatic lymph nodes in the draining basin.