The aim of this study was to evaluate the diagnostic performance of ultrasonography (US)-guided core biopsy of a supraclavicular lymph node (SCN) for detecting metastasis and epidermal growth factor receptor (EGFR) mutations. We included 229 patients who underwent US-guided core biopsy of SCN with lung cancer from January 2011 to December 2013. We evaluated the morphologic characteristics and measured the sizes of SCNs on US and chest computed tomography (CT). The clinical stage, maximum standardized uptake value (SUV max) on 18F-fluorodeoxyglucose positron emission tomography, and the morphology on US and CT in the positive metastasis were compared with those in the negative metastasis. The prevalence of EGFR mutations of the adenocarcinoma and procedure-related complication was investigated. The accuracy of US-guided core biopsy of SCN diagnosing metastasis was 97.8% (224/229). The cutoff values (sensitivity; specificity; area under the receiver operating characteristic curve, 95% confidence interval [CI]) of the short-axis dimension of SCN on CT were 0.85 cm (72.3%; 80.6%; 0.808, 95% CI: 0.740-0.875), on US 0.75 cm (73.5%; 84.8%; 0.843, 95% CI: 0.788-0.897), and that of SUV max 4.05 (79.1%; 81.8%; 0.853, 95% CI: 0.780-0.925). The mutations were positive in 35.8% with adenocarcinoma. There were no procedure-related complications of US-guided SCN core biopsy. US-guided SCN core biopsy is a reliable and safe method for detecting metastasis, histologic subtyping, and identifying the EGFR mutation in the advanced lung cancers. It may be a substitute for more invasive lung biopsy as an initial tissue confirmation in the advanced disease.