Lung cancer in the young, which has the characteristics of a higher incidence of adenocarcinoma, lower male-to-female ratio of the patients, and less frequent smoking history in the patients, may possibly be associated with genetic predisposition to cancers. We studied six microsatellite loci (D2S123, D3S659, D3S966, D5S346, WT1, and TP53) in 18 surgically treated lung cancer patients aged 25-40 years and nine control patients aged 62-74 to determine the presence of microsatellite instability (MSI) and to correlate its occurrence with clinicopathological characteristics. Of the 18 patients, 11 were female and seven were non-smokers. There were 15 adenocarcinomas and three squamous cell carcinomas, 15 (83%) of which had vascular invasion. MSI was positive in seven (39%) of 18 young patients and one (11%) of nine control patients. Moreover, MSIs in a half or more of six loci examined were demonstrated in five (28%) young patients, whereas no control patients showed such a high frequency of MSI. We observed no significant differences in clinical or pathologic parameters between cases with and without MSI. This result suggests that genetic factors play an important role in the development of lung cancer in young adults.