PURPOSE: To assess the diagnostic role of FNA, PCNB, and a combination of both methods in patients who underwent percutaneous transthoracic biopsy for a malignant or benign intrathoracic lesion. MATERIALS AND METHODS: We retrospectively reviewed the findings of 213 patients with an intrathoracic mass or consolidation who underwent FNA (Group A, n=98), PCNB (Group B, n=31) or a combination of both methods (Group C, n=84). Under fluoroscopic guidance, diagnoses were based on the findings of surgery, biopsy at another site or clinical and radiologic follow-up. In the differential diagnosis of benign and malignant disease, and in the diagnosis of small-cell lung cancer, pulmonary tuberculosis, non-tuberculous infectious disease and benign mass, sensitivity, specificity and accuracy were statistically analysed in each group. RESULTS: Among 213 patients, lesions were malignant in 134 and benign in 79. In group A, sensitivity and specificity were 90.1% and 100% for malignant lesions, and 91.5% and 90.1% for benign, while in group B, the corresponding findings were 90.4% and 100%, and 90.0% and 90.1%. In group C, corresponding rates of 95.1% and 100% (p<0.05) and 100% and 92% (p<0.05) were recorded. In group C, accuracy and sensitivity were higher than in group A or (p<0.05). Post-procedural pneumothorax occurred in 15.3% of group A, 13.3% of group B, and 20.6% of group C, while hemoptysis was found in 7.1% of group A, 13.3% group B, and 2.9% of group C. Among the three groups, the complication rate showed no statistically significant variation (p<0.05). In the specific diagnosis of small-cell lung cancer, the sensitivity and specificity of FNA and PCNB were, respectively, 100% and 98.5%, and 90.0% and 98.0% (p<0.05) ; for tuberculosis, the corresponding figures were 35.0% and 100%, and 20.0% and 97.2 (p<0.05). FNA was better in the diagnosis of non-tuberculous infectious disease, while PCNB was better in the specific diagnosis of benign masses, without statistical significance. Conclusion: FNA is superior to PCNB in the diagnosis of tuberculosis and the differentiation of small cell lung cancer, and is thus the indicated initial approach for the majority of patients who are to undergo transthoracic bigosy. A combination of FNA and PCNB can provide more accurate differentiation between malignant and benign thoracic disease, without increasing the complication rate, than can one method used alone.