KRAS belongs to a family of small GTPases and gain-of-function mutations in the gene yield a constitutively active protein. Such mutations are found in approximately 30% to 50% of metastatic colorectal cancers and are common in other tumor types. The most frequent KRAS mutations occur at codons 12, 13, and 61. Mutations at codons 117 and 146 are less common. Mutations at codon 14 have been detected in adenocarcinomas of the small intestine and colon as well as AML. Germline V14I mutations have been identified in patients with Noonan syndrome. In vitro studies have shown that V14I mutations lead to moderately enhanced MEK1/2 and ERK1/2 phosphorylation suggesting increased downstream signaling, but with slightly less transforming capacity than G12D mutation. Mutations in the KRAS gene may indicate poor prognosis and poor drug response to EGFR-targeted therapies. Results should be interpreted in conjunction with other laboratory and clinical findings.