A prospective study to compare the safety and diagnostic accuracy of ultrasonographically guided transthoracic large-bore cutting biopsy histologic examination with fine-needle aspiration cytologic examination was conducted in 149 patients with thoracic tumors (29 mediastinal tumors and 120 pulmonary masses). The authors found that large-bore cutting biopsy under ultrasonographic guidance could be as safe as fine-needle aspiration, whereas diagnostic accuracy was significantly higher (97% versus 59% in malignant tumors, respectively, P less than 0.05; 85% versus 33% in benign lesions, respectively, P less than 0.05). The size, depth, and location of lesions did not influence the results of transthoracic needle aspiration or cutting biopsy. In 77 patients with primary lung cancer, fine-needle aspiration cytologic examination, although achieving 88% positive cytologic results, identified the histologic cell type accurately in only 70%, whereas Tru-Cut (Top Surgical, Tokyo, Japan) biopsy was 97% accurate in confirmative histologic diagnosis. Fourteen patients had discordant cytologic and histologic diagnoses, and the cases of 3 (3.9%) were between small cell lung cancer and non-small cell lung cancer. The diagnostic accuracy of Tru-Cut biopsy also was significantly higher than that of fine-needle aspiration in metastatic cancers (90% versus 33%, respectively) and mediastinal tumors (100% versus 46%, respectively). The authors conclude that transthoracic cutting biopsy under ultrasonographic guidance is safe and has a higher diagnostic accuracy as compared with fine-needle aspiration. This technique is particularly useful for benign lesions or tumors with pleomorphic morphologic characteristics, such as lymphomas and thymomas.