Two hundred and eighteen patients, with thoracic tumors larger than 3 cm in size, underwent ultrasound-guided percutaneous transthoracic core biopsy with a large-bore Tru-Cut needle. Fifty-five tumors were in the mediastinum, and 122 tumors were located at subpleural area, and 42 tumors were within the lungs. In 122 subpleural tumors, the sensitivity of ultrasound-guided core biopsy for the diagnosis of malignancy was 96.8%, and accuracy was 97.5%. Sensitivity for the diagnosis of malignant tumors located within the lungs was 94.6%, and accuracy was 95.2%. In 54 patients with mediastinal tumors, definite histologic diagnosis could be obtained in 48 patients (88.9%). The sensitivity of ultrasound-guided biopsy for the diagnosis of malignancy in these 48 mediastinal tumors was 97.1%, with an accuracy of 97.9%. Three patients had complications with minimal pneumothorax and one with mild hemoptysis. We conclude that percutaneous transthoracic core biopsy with Tru-Cut needle under ultrasound guidance is a safe and sensitive way to obtain specimens for accurate histologic diagnosis of thoracic tumors. The diagnostic yield is high, and the technique, relatively simple, can also be used for outpatients.