To evaluate whether thrombomodulin (TM) can be considered a tumor marker of lung cancer, we examined serum TM levels in 179 lung cancer patients by an enzyme immunoassay. Further, in 91 resected cases, we also investigated the TM presence in lung cancer tissue by an immunohistochemical method. Our findings revealed that 58 (32%) of 179 lung cancer patients had higher serum TM levels than our cutoff levels. No difference was seen in the serum TM-positive ratio between histologic types, but patients with Stage IV disseminated cancer showed a higher serum TM-positive ratio than those with Stage I-IIIB localized cancer, especially cases of adenocarcinoma. Immunostaining results showed a TM presence in the cancer cells of 32 (35%) of 91 lung cancer cases. The TM presence in cancer cells was higher in cases with squamous cell carcinoma than with adenocarcinoma; no differences were seen among the disease stages. No correlation was found between the serum TM and the presence of TM in cancer cells. Further, serum TM status appears to have little clinical significance as a method to detect early lung cancer or for predicting the recurrence after the surgical excision of a lung cancer. Thus, we have concluded that, although serum TM levels are elevated in some lung cancer patients, it is doubtful that the TM status is useful as a tumor marker of lung cancer.