Xanthine dehydrogenase (XDH), also known as xanthine oxidoreductase (XOR), has long been recognized as the key enzyme in the catabolism of purines, oxidizing hypoxanthine into xanthine and then xanthine into uric acid. In addition, levels of XDH expression are reportedly related to the prognosis of patients with malignant tumors, though the relationship between the clinicopathological features of lung cancer and XDH is not fully understood. We therefore used semiquantitative real-time reverse transcription polymerase chain reaction to assess expression of XDH mRNA in tumor samples from 88 patients with adenocarcinoma of the lung. We then correlated XDH mRNA levels with known clinicopathological factors. We found that the 5-year overall survival rate among patients strongly expressing XDH was significantly poorer than among those expressing lower levels of XDH (P < 0.001; log-rank test). Normal lung tissue does not express XDH. Multivariate Cox proportional hazard analyses revealed that being male (hazard ratio, 3.14; 95 % confidence interval (CI), 1.45-7.07; P = 0.004), nodal metastasis positivity (hazard ratio, 5.74; 95 % CI, 1.94-19.3; P = 0.001), and high XDH expression (hazard ratio, 2.33; 95 % CI, 1.11-5.02; P = 0.026) were all independent factors affecting 5-year disease-free survival. In conclusion, high tumoral XDH expression is an independent predictor of a poor prognosis in patients with adenocarcinoma of the lung.