OBJECTIVES: The objective of this study, as part of the Center for Comparative Effectiveness Research in Cancer Genomics (CANCERGEN), was to establish and evaluate a process for incorporating formal value of research (VOR) analyses into a stakeholder-informed research prioritization process for genomic applications for study in a prospective, randomized comparative effectiveness trial within the SWOG clinical trials cooperative.  METHODS: Six candidate genomic applications, identified through a landscape-analysis, were prioritized by 13 stakeholders based on 9 criteria: population impact, adequacy of standard care, analytic and clinical validity, benefits, harms, economic impact, evidence of need, clinical trial feasibility, and market factors.  We developed decision-analytic based models for the top three candidates, performed expected value of perfect information calculations, and presented the results to stakeholders.  We evaluated the impact of the VOR analyses on the test ranking and stakeholder perceptions about the usefulness of VOR using an online survey.  RESULTS: The top three genomic applications based on the initial rankings were: 1) ERCC1 testing in early stage non-small cell lung cancer (NSCLC), 2) EGFR mutation testing in advanced NSCLC, and 3) tumor marker testing to detect recurrence in early stage breast cancer (BC).  The VOR was estimated to be: $2.2 to $2.8 billion, $33 million, and $2.1 billion, respectively.  After presentation of the results, the stakeholders changed their ranking to 1) ERCC1, 2) BC markers, and 3) EGFR.  The majority of stakeholders found the VOR information to be useful (69%), with 53% changing their ranking after consideration of the VOR findings.  In addition, all stakeholders indicated that they would use VOR analyses in future research prioritization processes.  CONCLUSIONS: Stakeholder-informed research prioritization of genomic applications is a function of many evidence domains.  Our study suggests that with adequate resources, VOR analyses can be incorporated into this process and provide useful information for research prioritization.