To evaluate the outcome of percutaneous lung biopsy (PLB) findings using cone-beam computed tomographic (CT) guidance (CBCT guidance) and compared to conventional biopsy guidance techniques. CBCT guidance is a stereotactic technique for needle interventions, combining 3D soft-tissue cone-beam CT, needle planning software, and real-time fluoroscopy. Between March 2007 and August 2010, we performed 84 Tru-Cut PLBs, where bronchoscopy did not provide histopathologic diagnosis. Mean patient age was 64.6 (range 24-85) years; 57 patients were men, and 25 were women. Records were prospectively collected for calculating sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. We also registered fluoroscopy time, room time, interventional time, dose-area product (DAP), and complications. Procedures were divided into subgroups (e.g., location, size, operator). Mean lesion diameter was 32.5 (range 3.0-93.0)mm, and the mean number of samples per biopsy procedure was 3.2 (range 1-7). Mean fluoroscopy time was 161 (range 104-551)s, room time was 34 (range 15-79)min, mean DAP value was 25.9 (range 3.9-80.5)Gy·cm(-2), and interventional time was 18 (range 5-65)min. Of 84 lesions, 70 were malignant (83.3%) and 14 were benign (16.7%). Seven (8.3%) of the biopsy samples were nondiagnostic. All nondiagnostic biopsied lesions proved to be malignant during surgical resection. The outcome for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy was 90% (95% confidence interval [CI] 86-96), 100% (95% CI 82-100), 100% (95% CI 96-100), 66.7% (95% CI 55-83), and 91.7% (95% CI 86-96), respectively. Sixteen patients (19%) had minor and 2 (2.4%) had major complications. CBCT guidance is an effective method for PLB, with results comparable to CT/CT fluoroscopy guidance.