Background: Accurate classification of non-small cell lung cancer (NSCLC) using morphological features has several limitations. However, the use of thyroid transcription factor 1 (TTF-1) and Napsin A as markers for the identification of various subtypes of NSCLC has shown promise. This meta-analysis was designed to evaluate the diagnostic value of combined TTF-1 and Napsin A test to distinguish lung adenocarcinoma from squamous cell carcinoma. Methods: The Medline, EMBASE and Web of Science databases were searched, along with the reference lists of relevant articles (up to May 4, 2014). Ten studies containing 1,446 subjects were identified. The sensitivity, specificity, diagnostic odds ratio (DOR) and area under the summary receiver operating characteristics curve (AUC) were calculated to estimate the combined diagnostic value of TTF-1 and Napsin A. Results: The pooled sensitivity and specificity were 0.76 (95% CI: 0.69-0.83) and 1.00 (95% CI: 0.92-1.00), respectively. The positive and negative likelihood ratios were 877.60 (95% CI: 8.40-91533.40) and 0.24 (95% CI: 0.18-0.32). The DOR was 3719 (95% CI: 33-414884). The AUC was 0.92 (95% CI: 0.89-0.94). The patient's location was a source of heterogeneity for sensitivity. The patient's location, the study's sample size and the threshold used to determine positive staining were consistently found to be sources of heterogeneity for specificity in subgroup analyses and meta-regression. Conclusions: The combined test of TTF-1 and Napsin A presents a promising alternative method, useful to distinguish between lung adenocarcinoma and squamous cell carcinoma.