To assess the value and limitations of fine-needle aspiration (FNA) and core needle biopsy (CNB) in the diagnosis of intrathoracic lesions, we retrospectively compared the diagnostic accuracy of 362 FNA and concurrent CNB procedures performed on 350 patients. Based on the final diagnoses that were determined based on combined information from biopsy, resection, clinical, radiologic, and microbiologic findings, the study cases were grouped into 188 malignant, 161 benign, and 13 inconclusive lesions. FNA and CNB yielded similar diagnostic accuracy for malignant tumors (85.1% vs 86.7%) and epithelial malignant neoplasms (86.4% vs 85.2%), whereas CNB yielded better diagnostic accuracy (96%) than FNA (77%) for nonepithelial malignant neoplasms. Combined FNA and CNB substantially improved the rate of malignancy diagnosis (95.2%). Of 161 benign cases, 50 were proven to be benign-specific lesions; FNA provided specific diagnosis in 20 (40%) and CNB in 46 (92%). The remaining 111 benign lesions yielded benign-nonspecific findings on both specimens. These results indicate that CNB should be obtained when clinical or radiologic findings do not match the cytologic findings or nonepithelial lesions and benign lesions are considered likely.