Computed tomography (CT) was used to guide percutaneous fine-needle biopsy in 150 cases of difficult thoracic lesions; in 76 cases, nondiagnostic bronchoscopy (n = 62) and fluoroscopic biopsy (n = 14) had previously been performed. CT was indicated for guidance when the pulmonary or pleural lesions were small (0.3-2.5 cm); in a juxta-vascular location, either hilar or mediastinal; not seen or poorly visualized on conventional radiographs; or considered inaccessible. A diagnosis was made in 124 of 150 cases (82.7%) (107 of 124 malignant and 17 of 26 benign lesions), including 86 of 107 lung nodules (80.4%), 28 of 31 mediastinal lesions (90.3%), and ten of 12 pleural masses (83.3%). Complications included pneumothorax (n = 64), hemoptysis (n = 5), hemothorax (n = 2), and pericarditis (n = 1). The high rate of pneumothorax, its treatment, and advantages of its immediate radiologic management are discussed. Use of CT guidance considerably expands the scope of thoracic lesions amenable to percutaneous biopsy.