Malignant pleural effusion of lung cancer is an important prognostic factor, even in minor effusions. Previous studies reported that cytological examination could not detect malignant cells in pleural dissemination cases. Therefore, we used real-time PCR as a more sensitive test to detect malignant cells. The subjects were selected from 132 primary lung cancer patients and 8 benign tumor patients as negative control. These subjects had no apparent pleural effusion or distant metastasis. All subjects were negative on cytological examination and without exfoliation evidence. The follow-up duration was 18.1 +/- 7.1 months (mean +/- SD). In the real-time PCR, the CEA-mRNA and GAPDH-mRNA parameters were measured simultaneously, and the CEA-mRNA ratio was obtained as normalized values of CEA-mRNA divided by GAPDH-mRNA. The CEA-mRNA ratio in our study was correlated with lymph node metastasis (N-factor: p = 0.0948) and lymphatic invasion (Ly-factor: p = 0.0520). Using a proportional hazard model, with recurrence or death as terminal point, the CEA-mRNA ratio affected the recurrence risk by 1.920 (95% CI: 1.104-3.340) in Stage 1a. Using log rank testing, we found significant differences in the recurrence rate between the CEA-mRNA-positive and -negative cases (p = 0.0039) at cut-off point 0.1.