Abstract: Objective: To evaluate the significance of tumor marker CEA, NSE and CYFRA21-1 adopted alone or in combination in the diagnosis of lung cancer meningeal metastasis. Methods: Thirty-five patients with lung cancer meningeal metastasis and 35 patients with benign brain tumor were studied. The diagnosis was based on neurological examination, MRI scan, and presence of neoplastic cells in the cerebrospinal fluid (CSF). Tumor marker levels in CSF and serum were measured by electrochemiluminescence technique(Elecsys 170, Roche). Results: CSF and serum tumor marker levels were significantly higher in patients with lung cancer meningeal metastasis than in patients with benign disease (P<0.01). In the CSF of the 35 patients with lung cancer meningeal metastasis, the level of all of the three tumor markers was higher than that in the controls (P<0.01). The cut-off values of tumor markers in the serum were determined according to the lab standard. The values of CEA, NSE and CYFRA 21-1 were 5μg/L, 15.2μg/L and 3.3μg/L, respectively. To determine optimal cut-off values of tumor markers in CSF, receiver operating characteristic (ROC) curve was used. The cut-off values of CSF concentration of CEA, NSE and CYFRA 21-1 were 4.7μg/L, 14.6μg/L and 5.5μg/L, respectively. The sensitivity and specificity of CEA, NSE and CYFRA21- 1 in CSF were 91.4% and 91.4%, 51.4% and 94.3%, and 82.9% and 97.1%, respectively. When at least one tumor marker in CSF was positive in patients with lung cancer meningeal metastasis, the sensitivity of it was 100%. When all of the three tumor markers were positive, the specificity was 100%. Conclusion: These three tumor markers are valuable auxiliary parameters in diagnosing lung cancer meningeal metastasis. The combination of CEA, NSE and CYFRA21-1 is more valuable for diagnosis. It may be a complementary method in diagnosing patients without visualized tumor by cytological examination and MRI. The above results need further investigation in a larger group of patients.