PURPOSE: To assess the clinical utility of ultrasound (US)-guided core-needle biopsy (CNB) of the mediastinum performed with a one-hand automatic-sampling technique. MATERIALS AND METHODS: Diagnostic or pathologic findings of US-guided CNBs performed with 14- or 18-gauge needles in 62 biopsies of mediastinal lesions were reviewed. RESULTS: An average of 2.4 punctures were performed at each biopsy session. A specimen sufficient for diagnosis was obtained in 52 of 62 biopsies (84%). There were no serious complications. CONCLUSION: When a mediastinal tumor is visible at US, US-guided CNB of the mediastinum is an accurate and safe technique. The method is a simple and cost-effective alternative to more invasive techniques such as mediastinoscopy or open diagnostic surgery.