BACKGROUND:The status of regional lymph nodes (LNs) is one of the most consistent predictors of survival in Merkel cell carcinoma (MCC). In cases of clinically localized disease, current practice involves sentinel lymph node (SLN) assessment. OBJECTIVES:To propose ultrasonography (US) followed by fine needle aspiration cytology (FNAC) and immunohistochemistry as a useful diagnostic tool in the pre-surgical management of patients with MCC. METHODS:US of LNs was performed in 75 patients with MCC (22 with stage III tumours; 53 with stage I-II). In patients with US suspected disease, US coupled with FNAC of the LN was performed. Smears were examined by routine cytological staining supplemented with immunohistochemical staining for cytokeratin 20. All patients underwent surgical removal of regional LNs. RESULTS:In all 22 patients with stage III tumours, US was indicative of tumour deposits and FNAC confirmed metastases to LNs. In 11 of 53 patients with localized MCC without clinical evidence of nodal disease, US revealed enlarged, equivocal nodes where FNAC was performed. Ten LNs were cytologically positive for metastases, and one was negative. Upon histological examination, the FNAC-negative case showed a metastasis 5 mm in diameter. In all the other 42 cases with no clinical or US evidence of LN involvement, only SLN biopsy was performed and in six cases small metastatic foci were detected. Ultimately, of the 53 stage I-II MCC, 17 had positive LN involvement. In 10 cases (59%) metastases were detected by FNAC, and in seven cases, were detected by SLN biopsy. CONCLUSIONS:In a selected subset (∼20%) of patients with MCC with clinically localized disease, US followed by FNAC in the suspect LN is a valid alternative to the classical protocol of SLN histological examination.