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To investigate the diagnostic value of ultrasound-guided core needle biopsy (US-CNB) in suspected cases of lymph node metastasis from cutaneous melanoma. All patients with cutaneous melanoma followed in Saint-Louis Hospital between 2006 and 2010 who underwent US-CNB for suspicion of melanoma lymph node metastasis were reviewed retrospectively. Histopathological results of US-CNB samples were classified as melanoma, other malignancy, suspicious, inadequate, or benign. The diagnostic accuracy of US-CNB was assessed by comparison with two reference standards: histopathological examination of the radical lymph node dissection or, when this was not available, clinical and radiological follow-up. The data from 72 US-CNB were analyzed. Forty-four melanomas, 22 benign, three other malignancies, three inadequate samples, and no inconclusive specimens were diagnosed. Seventy-one US-CNB results were confirmed (98.6%). US-CNB achieved high sensitivity, specificity, and positive predictive value (respectively, 97.9, 100, and 100%). No adverse events were reported after the procedure. US-CNB provided a mean tissue volume of 16.7 mm3 per lymphadenopathy. US-CNB has diagnostic value similar to that of fine-needle aspiration cytology. It represents a reliable alternative method in melanoma lymph node metastasis to avoid surgery in patients who will not benefit from it. US-CNB provides relatively large samples of tissue suitable for comprehensive genomic analyses currently needed for research and personalized care of melanoma patients.