OBJECTIVE To explore the clinical significance of the human telomerase reverse transcriptase (hTERT) mRNA, CEA and CA19-9 in differential diagnosis of benign and malignant pleural effusions.METHODS Concentrations of CEA and CA19-9 in pleural effusions were assayed using automated chemiluminescence, and expression of hTERT mRNA was detected by RT-PCR.RESULTS The positive rates of hTERT mRNA, CEA and CA19-9 expression in the group with malignant effusions were significantly higher compared to the group with benign effusion(P ＜ 0.05). The sensitivity (%), specificity (%) and diagnostic accordance rates (%) of the 3 tumor markers were as follows: I)hTERT mRNA: 81.8/90.5/86.1; ii) CEA: 52.3/92.9/72.1; iii) CA19-9:34.1/90.5/61.6. The positive rates of hTERT mRNA + CEA (%)expression in the pleural effusions were 97.7.CONCLUSION All of these tumor markers can be helpful for differential diagnosis of pleural effusions, hTERT mRNA had more clinical value in differentiation of the pleural efffusions.CA19-9 is unfit to be as an optimal index. The combined assay of hTERT mRNA and CEA in pleural effusions can further raise the positive detection rate of the tumor markers and can be helpful in producing a diagnosis.