Abstract: Objective To explore the clinical value of CT-guided percutaneous needle biopsy (PCNB) for diagnosis of atypical pulmonary tuberculosis. Methods The data from 15 patients undergoing diagnostic PCNB for pulmonary tuberculosis were retrospectively analyzed. Prior to PCNB, definitive diagnosis failed to be obtained from other examinations including sputum smear in 10 cases, fiberoptic bronchoscopy in 12, chest X-ray in 13, CT scan in 15, and position emission tomography (PET) with CT examination in 1 case. Results Sputum smears and fiberoptic bronchoscopy both failed to produce positive results and pulmonary and/or mediastinal lesions were shown by chest X-ray, CT, and PET-CT. Pulmonary tuberculosis were diagnosed in the 15 cases by histopathological examination following PCNB, and pneumothorax in relation to PCNB occurred in 3 cases and hemoptysis in 1 case. Conclusion PCNB provides a safe and accurate means for diagnosis of pulmonary tuberculosis when imaging and other diagnostic modalities fail to result.