A series of clinically requested colorectal cancer cases were evaluated for KRAS mutation status comparing traditional bidirectional Sanger dideoxysequencing and Taqman Mutation Detection Assay using Competitive Allele Specific Taqman PCR (TMDA CastPCR).  All samples requested prospectively and a series of previous cases with known or ambiguous sequence mutations were compared using the two different methods.  The concordance between the two methods is defined and limits of detection for each demonstrated- showing the need to carefully evaluate tumour content as a means of triaging cases in a clinical workflow.  The TMDA CastPCR method offers a number of benefits over standard sequencing technology to investigate clinically relevant KRAS (and BRAF) mutations in CRC cases- including 1) specificity for the targeted clinically relevant assays, 2) sensitivity for low proportion tumour cases such as post treatment resections and some metastatic lesion samples, 3) a fast turn-around of results and 4) good concordance with Sanger sequencing and other methods.  Due to the specific nature of this technology this method is unable to detect rare and unusual mutations not tested within the targeted series of selected mutation assays.  However, in combination with a screening system such as HRM and triaging of cases based on tumour proportion, TMDA CastPCR represents and useful, cost effective technology for rapid and sensitive detection of the clinically relevant mutations in colorectal or other cancer samples in a clinical laboratory workflow. This technology also offers the flexibility to easily upgraded to new targeted assays in these and other genes such as NRAS, PIK3CA and an array of other genes within the cancer pathways.