Recently DNA mismatch repair system (MMR) has been extensively investigated in molecular medicine. Microsatellite (MS) DNA alterations are considered as indicating an ineffective MMR system. MS loss of heterozygosity (LOH) and microsatellite instability (MSI) have been reported in a number of human malignancies. LOH and MSI have recently been detected in benign diseases, such as actinic keratosis, pterygium and atherosclerosis. In addition, MSI and LOH have been detected in asthma, chronic obstructive pulmonary disease, sarcoidosis and idiopathic pulmonary fibrosis. This is a review of MSI in benign lung diseases. It is concluded that detecting genetic alterations at the MS DNA level could be a useful technique to identify locus of potential altered genes that may play a key role in the pathogenesis of these diseases. In addition, MSI and LOH could be used as a genetic screening tool in molecular epidemiology.