Lung cancer, like other cancers, is considered to develop through the 
accumulation of genetic alterations. Mutation of the KRAS gene is one of the 
most important events in carcinogenesis of the lung. The KRAS gene, belonging to 
the RAS gene family, encodes a membrane-bound 21-kd guanosine triphosphate 
(GTP)-binding protein. Single point mutations in this protein result in 
continuous activation to transmit excessive signals, promoting a variety of 
biological events. In lung cancers, the mutations concentrate at codon 12 and 
mostly affect adenocarcinomas (ADCs). They also affect atypical adenomatous 
hyperplasia, the precursor of ADCs. Therefore, mutation of the KRAS gene is 
suggested to confer a growth advantage to airway epithelial cells enabling them 
to expand clonally early in the development of ADCs. The mutation is also a 
reliable marker of an unfavorable response to certain molecular-targeting 
therapies. Furthermore, patients with ADCs affected by mutations have been 
reported to exhibit a significantly higher risk of postoperative disease 
recurrence. Thus, the significance of KRAS gene mutations has been investigated 
extensively. However, not all the details emerged. In this review, particulars 
that have been established are introduced, and important issues remaining to be 
resolved are discussed, with special reference to carcinogenesis of the lung.