Using the one-step sandwich enzyme immunoassay for pro-MMP2, we investigated whether the serum pro-MMP2 levels could be used as predictors of the development and extension of lung cancer. The study included 52 lung cancer patients and 26 nonmalignant thoracic disease patients. Serum samples were collected before clinical treatment. The serum pro-MMP2 levels were found to be elevated in patients with lung cancer (1006.3+/-37.4 ng/ml) in comparison with nonmalignant controls (767.7+/-41.6 ng/ml) (P = 0.0002). In addition, stage IIIb lung cancer patients (1167.2+/-124.2 ng/ml) had significantly higher pro-MMP2 levels compared with stage I patients (936.0+/-44.8 ng/ml, P = 0.0431). The serum pro-MMP2 levels were similar in the samples between the pathological subtypes. As a result, the serum pro-MMP2 levels may serve as a marker that can be used as a diagnostic indicator of higher stages in lung cancer. There was no difference in the prognosis between the group with normal pro-MMP2 levels (<850 ng/ml) and the group of elevated pro-MMP2 levels (>850 ng/ml), thus indicating that serum analyses of the pro-MMP2 levels were of limited value in the prognosis of lung cancer.