Caspase-cleaved cytokeratin 18 fragments (M30 antigen) can be detected in the circulation of patients with carcinoma and are believed to reflect cell death of tumors of epithelial origin. M30 antigens cleaved at Asp396 are detected using an epitope-specific antibody (M30 antibody). We here measured the levels of such fragments in patients with lung cancer (n=60), patients with benign lung disease (n=22) and healthy control subjects (n=32). A statistically significant difference was observed between these groups (p<0.001; Kruskal-Wallis). Basal M30 antigen levels were evaluated with regard to their predictive power of survival. The best cut-off value for M30 antigen level for the prediction of death was 43.8 U/L. Patients with basal M30 antigen levels higher than 43.8 U/L had significantly shorter median survival than those with lower basal M30 antigen levels (p=0.013; hazard ratio: 3.9) (95% CI=1.3-11.4). To determine whether cytotoxic therapy increases serum M30 antigen in lung cancer patients, we monitored the levels of M30 antigen in 18 lung cancer patients before chemotherapy and after 24 and 48 h. An approximately four-fold increase in M30 antigen levels was observed at 48 h (p<0.001). These results suggest as a first time that serum M30 antigen might be used as a novel biomarker for prediction of survival as well as for monitoring the efficiency of chemotherapy in lung cancer patients.