Activating mutations in the KRAS gene occur in approximately 40% of colorectal carcinomas, 20% of non-small cell lung cancers, and a variety of other human cancers. Mutations are predominantly single nucleotide substitutions (missense mutations), most frequently occurring within codons 12 and 13 of exon 2. Less commonly, mutations occur within codon 61 of exon 3 and codons 117 and 146 of exon 4. Collectively these mutations have been associated with a limited clinical response to epidermal growth factor receptor (EGFR) targeted therapies in lung and colorectal cancers, and may also have prognostic implications. This DNA test is performed by targeted next-generation sequencing to detect mutations within sequenced regions of KRAS exons 2, 3, and 4 (NM_33360.3; Hg19 chr12:25398205-25398304, chr12:25380261-25380349, chr12:25378550-25378658) including codons 12, 13, 61, 117, and 146. Specimens should contain an adequate proportion of neoplastic cells (>20%) in the area to be extracted to ensure mutation detection.