Background: Genomic and personalized medicine (GPM) applications have the potential to enhance our ability to screen for disease predisposition and treatment responsiveness. Testing colorectal cancer (CRC) tissue for mutations in the KRAS gene is one such test that can help oncologists decide how to treat patients with metastatic colorectal cancer (mCRC). KRAS testing is already standard clinical practice in many settings and allows oncologists to tailor the use of anti-EGFR therapy to increase treatment effectiveness and potentially minimize adverse events. The FDA has also changed the labeling of these therapies indicating they are not effective for treatment of patients with KRAS mutations. Methods: This study evaluates the characteristics of patients, providers, and health systems as they relate to the diffusion and utilization of KRAS testing. A comparative analysis of KRAS testing for mCRC patients treated in community practices to evaluate its effectiveness in terms of both progression-free survival and overall survival will also be conducted. Total sample includes 800 mCRC cases diagnosed between January 1, 2005 and July 31, 2010 from 7 different sites. Electronic medical record data at each site captures information on patient characteristics including disease characteristics, comorbidities, history of all cancer-directed therapies, acute complications, receipt of palliative care and contextual socioeconomic variables. Chart review data will supplement and verify the electronic data. Conclusions: This study will serve as a model for evaluating the potential impact of GPM applications to improve health outcomes, reduce costs, and influence patient and physician decision-making in the area of personalized therapies.