Tumor markers were used for disease monitoring in lung cancer patients. The goal of this pilot study was to determine the diagnostic efficiency of a new tumor metabolic marker, Tumor M2-pyruvate kinase (Tumor M2-PK) for the detection of tumor growth in inoperable lung cancer patients.Fifty-seven consecutive and primary inoperable lung cancer patients were included in this prospective study. Changes in plasma levels of Tumor M2-PK were compared to the clinical course of the disease. Clinical monitoring was evaluated according to the standard criteria of the WHO. Of the 57 patients, 19 were in remission, 18 showed signs of stable disease and there were 20 tumor progressions under therapy. In the further follow-up after treatment, tumor relapse occurred in 30 patients. Tumor M2-PK was measured in plasma before and after treatment as well as at time of relapse. During tumor remission Tumor M2-PK levels decreased significantly under treatment (P=0.0004). As might be expected, pre- and post-treatment marker concentrations did not differ significantly in patients with stable disease. In progressive lung cancer patients a significant increase in Tumor M2-PK was detectable (P=0.0094). Overall, a decrease of Tumor M2-PK was seen in 17 (89%) of all responders, while an increase could be detected in 16 (80%) of the patients experiencing tumor progression. After treatment tumor relapse occurred in 30 patients. Tumor M2-PK increased significantly (P=0.0201) at time of relapse in 17 patients with non-small cell lung cancers and exceeded the cut-off in 11 of the 17 (65%). In conclusion, Tumor M2-PK proved useful as a diagnostic aid for therapy control in lung cancer patients. This marker can also be used to detect tumor relapse after treatment. Tumor M2-PK could be well suited to complete the present diagnostic panel for monitoring of inoperable lung cancer patients.