LUN is a novel RING finger protein that is highly expressed in the lung and might be a transcriptional regulator of E-cadherin [J. Biol. Chem. 276 (2001) 14004]. It might be possible that LUN plays important roles in the development and progression of lung cancer through regulating expression of E-cadherin, but no clinical study on LUN expression has been reported. In the present study, we quantitatively examined gene expression of the LUN in surgical specimens resected from non-small cell lung cancer (NSCLC) patients. In normal lung tissues, the LUN gene expression was down-regulated in smokers (the mean LUN/GAPDH ratios, 0.222 for non-smokers and 0.144 for smokers; P = 0.030). In addition, the mean LUN/GAPDH ratio in lung cancer tissues was significantly lower than that in normal lung tissues (0.072 versus 0.162; P < 0.001). In addition, the LUN gene expression was slightly down-regulated along with progression of primary tumors, and strongly down-regulated along with nodal metastases (the mean LUN/GAPDH ratios, 0.091 for pN0, 0.073 for pN1, and 0.034 for pN2 diseases; P = 0.001). These results suggested that LUN might play important roles in inhibition of nodal metastases as well as in suppression of smoking-related oncogenesis in NSCLC.