KRAS is a gene that encodes one of the several proteins in the epidermal growth factor receptor (EGFR) signaling pathway that is important in the development and progression of cancer. KRAS can harbor oncogenic mutations that yield a constitutively active protein. Such mutations are found in approximately 30% to 60% of small intestine adenocarcinomas and are common in other tumor types. The relevant KRAS mutation is in one of five codons (12 13, 61, 117 or 146). KRAS mutations in small intestine tumors are associated with higher pT classification and more frequent pancreatic invasion. The effect of KRAS mutations on drug therapy has not been well established in the literature, however it has been extensively studied in colorectal adenocarcinoma. Mutations in the KRAS gene may indicate poor prognosis and poor drug response with therapies targeted to EGFR in colon cancer, and the absence of a KRAS mutation predicts a greater likelihood of response to EGFR-targeted therapies and improved survival with such treatment. The presence of KRAS mutations in codon 12, 13 or 61 is associated with a high likelihood of resistance to therapies targeting EGFR in colon cancer. In addition, mutations at codons 117 and 146 may also be associated with reduced response to EGFR-targeted therapies in colon cancer. Results should be interpreted in conjunction with other laboratory and clinical findings.