The purpose of this analysis was to study the association between the quantity of free circulating DNA and clinical variables in 99 advanced non-small cell lung cancer patients (NSCLC). The quantification in the serum of the gene of the catalytic fraction of telomerase (hTERT) by RT-PCR was used as a reference of the total amount of free DNA in blood. Patients were treated with cisplatin and docetaxel. The median hTERT level for patients in stage IIIB was 70.7 ng/ml vs. 53.1 ng/ml in patients in stage IV (p= 0.35). There was no association between hTERT values and therapy response, 53.9 ng/ml in the complete response (CR) + partial response (PR) group vs. 54.1 ng/ml in the stable disease (SD) + progressive disease (PD) group (p=0.23). In the multivariate analysis, hTERT was an independent predictive variable for time to progression (TTP) Hazard ratio (HR) 2.0, CI 95% 1.2-3.4, p=0.009) and overall survival (OS) (HR 2.4 CI 95% 1.3-4.3, p=0.004). The analysis of TTP and OS with a cut-off of hTERT at 40 ng/ml revealed that patients about this level had statistically poorer TTP (4 vs. 7 months, p= 0.009) and OS (5 vs. 15 months, p<0.0001). In conclusion, in advanced NSCLC, high serum hTERT levels may be a poor prognostic indicator for TTP and OS.