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Background and Objectives: The clinical utility of the tumor marker serum S-100B has been described in determining prognosis, for early diagnosis of recurrence and for disease monitoring in melanoma patients. Sentinel node biopsy is increasingly used as staging procedure for patients with clinically localized melanoma. The aim of this study was to determine the value of serum S-100B in melanoma patients before and after sentinel lymph node biopsy., Methods: S-100B values were measured prior to sentinel node biopsy in 89 patients and during follow-up (median 41 months; range 7-73 months) in 88 patients. The detection limit is < or =0.08 microg/L. In our laboratory levels of 0.16 microg/L and above are classified as increased., Results: Twenty-four patients had tumor-positive sentinel nodes, 65 had tumor-free sentinel nodes. The median S-100B value prior to the operation was < or =0.08 microg/L for all patients. Sensitivity and specificity of S-100B to predict the tumor-status of the sentinel node were 13% and 98%, respectively. Eighteen patients developed a melanoma-related recurrence. Sensitivity for early diagnosis of recurrence was 55% and 33%, respectively for patients with a positive versus a negative sentinel node. Specificity was 100% in both patient groups., Conclusions: S-100B is not useful in predicting the tumor-status of the sentinel node, and questionable for early diagnosis of recurrence afterwards. Elevation of serum S-100B is highly specific for melanoma recurrence.