Background: Lung cancer leads cancer-related mortality in the world. The objective of the present systematic review was to compare fine-needle aspiration biopsy (FNAB) with core-needle biopsy (CNB) for diagnostic characteristics and yields for diagnosing lung cancer in patients with lung lesions. Methods: The MEDLINE and EMBASA databases (from January 1, 1990, to September 14, 2009), the Cochrane Library (to Issue 4, 2009), and selected guideline Web sites were searched for relevant articles. Results: For overall diagnostic characteristics (benign vs. malignant) of FNAB and CNB, the ranges of sensitivity were 81.3%–90.8% and 85.7–97.4% respectively; of specificity, 75.4%–100.0% and 88.6%–100.0%; and of accuracy, 79.7%–91.8% and 89.0%–96.9%. For specific diagnostic characteristics of FNAB and CNB (identifying the histologic subtype of malignancies or the specific benign diagnoses), the ranges of sensitivity were 56.3%–86.5% and 56.5–88.7% respectively; of specificity, 6.7%–57.1% and 52.4%–100.0%; and of accuracy, 40.4%–81.2% and 66.7%–93.2%. Compared with FNAB, CNB did not result in a higher complication rate (pneumothorax or hemoptysis). No study has yet compared the diagnostic yields of FNAB and of CNB for molecular predictive-marker studies in patients with lung lesions. Discussion and Conclusions: The evidence is currently insufficient to support a difference between FNAB and CNB in identifying lung malignancies in patients with lung lesions. Compared with FNAB, CNB m ight h ave a h igher s pecificity t o diagnose specific benign lesions. Well-designed, good-quality studies comparing FNAB with CNB for diagnostic characteristics and yields in diagnosing lung cancer should be encouraged.