Background: Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine neoplasm of the skin with a high propensity for early lymph node metastasis and subsequent distant spread. Optimal treatment and prognostic factors are poorly defined. Objective: The purpose of this study is to assess the prognostic and therapeutic relevance of sentinel lymphonodectomy in MCC. Methods: Five patients with biopsy-proven MCC underwent gamma-probe-guided sentinel lymphonodectomy assisted by lymphatic mapping. From each sentinel lymph node (SLN), a series of paraffin sections was histologically and immunohistochemically examined for the presence of micrometastases, which were then staged according to the recently published S classification. Results: Four of the 5 patients showed metastatic disease in the SLNs, 3 of which were classified as S-2, 1 as S-3. Only 1 of the Sa patients demonstrated additional positive nodes at completion lymphonodectomy. The patient staged as Sg refused a radical lymph node dissection and died within 1 year due to widespread metastasis. Conclusions: Sentinel lymphonodectomy is a low-morbidity procedure which enables an early detection and exact staging of regional lymph node metastases with potentially high prognostic and therapeutic relevance in MCC. Copyright (C) 2001 S. Karger AG, Basel.