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 S₂, 1 as S₃. Only 1 of the S₂ patients demonstrated additional positive nodes at completion lymphonodectomy. The patient staged as S₃ 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.