OBJECTIVES: The Center for Comparative Effectiveness Research in Cancer Genomics (CANCERGEN) is a multi-disciplinary, national consortium established to conduct CER in Genomics and Personalized Medicine (GPM). The objective was the evaluation and prioritization of GPM applications for study in a prospective, randomized CER trial. METHODS: Candidate GPMs were identified through a landscape-analysis of recent literature.  Initial candidates were examined by cancer genomics experts and study investigators to identify 5-7 GPMs for evaluation by a diverse group of external stakeholders, including representatives from patients groups, payers, test developers, state-funded public HTA programs and practicing oncologists. We developed Topic Briefs and Test Target Profiles assessing the following domains: population impact, current standard of care, clinical validity, potential benefits, potential harms, economic impact, evidence of need, trial feasibility and current payer status. RESULTS: We identified 43 studies from 183 GPMs based on our landscape-analysis, which were narrowed to 4 GPMs through feedback from cancer genomics experts; 2 additional GPMs were identified by investigators from our clinical trials consortium (SWOG). The 6 GPMs included: ERCC1 testing for platinum-chemotherapy in NSCLC, EGFR mutation testing for TKIs in NSCLC maintenance, tumor markers for breast cancer recurrence, EGFR FISH testing for 1st-line cetuximab in NSCLC, BRAF testing in colorectal cancer, and gene expression profiling in multiple myeloma. External stakeholders preliminarily identified the first 3 of these as most likely providing the greatest value of research. CONCLUSIONS: A rapid process for research prioritization involving literature evaluation, expert input, and stakeholder feedback is feasible with adequate resources and processes.  Elements include an organization facilitating collaboration between investigators with CER/clinical trials experience, and utilizing  systematic and timely evidence-assessment accessible to stakeholders.  Final selection of a GPM for study in a prospective CER trial will be based on quantitative value-of-information analyses, implementation feasibility, and funding mechanisms, including coverage with evidence development.