The most successful strategies in the management of melanoma have always been based on early diagnosis and timely surgical removal. Sentinel lymphonodectomy (SLNE) is the most reliable technique for the detection of melanoma micrometastases in regional lymph nodes. The micromorphometric S-classification, a routinely determinable surrogate of tumor burden in the sentinel lymph node (SLN), has high prognostic relevance. SIII metastases, defined by a depth of invasion (d) greater than 1 mm below the capsular level, imply a risk of more than 50% for the presence of nonsentinel lymph node metastases in the same basin and for the emergence of distant metastases within 5 years of follow-up. Corresponding risks with SI metastases (d </= 0.3 mm) and SII metastases (0.3 mm < d </= 1 mm) do not exceed 15%. The survival curve for patients with SIII metastases approaches that of patients in the pre-SLNE era who underwent delayed lymph node dissection for subsequently detected nodal macrometastases. The survival of patients with initially removed SI and SII metastases is much better, similar to that of patients with S0 metastases. This explains the significant survival benefit of SLN-guided surgery in the entire population of patients with melanomas thicker than 0.75 mm, although the outcome of the subgroup without nodal metastases is not influenced by SLNE.