Genetic alterations in the microsatellite DNA level have been successfully detected in sputum samples of patients with COPD and have been shown to be disease specific. Furthermore, previous studies have shown that inflammation coexists in the nasal mucosa of patients with COPD. The aim of this study was to assess the presence of MSI in nasal cytological samples of patients with COPD comparing the results with sputum samples of the same individuals. Nasal brush samples, sputum samples obtained by induction, and peripheral blood from 20 patients with COPD were analyzed. DNA was extracted and analyzed for MSI using the following microsatellite markers: RH70958, D5S207, D6S344, D6S263, G29802, D13S71, D14S588, D14S292 and D17S250. Microsatellite analysis was also performed in 8 healthy non-smokers. MSI was detected in the sputum samples of 7 patients with COPD (35%). In contrast, no microsatellite DNA instability was noted in the nasal cytological samples of the same COPD patients. In addition, no genetic alteration was detected in the control group. These results suggest that MSI is a specific finding for the target organ of COPD, i.e. the lungs, despite the fact that inflammation coexists in the nasal mucosa of COPD patients. Our study supports the hypothesis that MSI could be an index of the somatic-acquired genetic alterations in the lungs of COPD patients.