Abstract The NIH Precision Medicine Initiative (PMI) is being designed to improve health care and outcomes through the delivery of individualized patient care. A long-term goal for PMI is to develop a new model for conducting research that engages participants, shares data responsibly, and ensures privacy. As a result of having a greater understanding of the complex ways in which biological, social, behavioral, and clinical factors interact in diverse populations, the PMI is also expected to lead to the development of individualized prevention and treatment strategies that reduce racial disparities in morbidity and mortality. To achieve this, it is essential that racial and ethnic minorities be included in PMI cohorts and research activities. However, the challenges associated with recruiting and retaining minorities in clinical research are well-documented; reduced access to and knowledge about clinical trials and other types of research are among the key barriers to minority participation. The NCI Community Oncology Research Program (NCORP) was designed to address barriers to minority participation in cancer clinical trials and cancer care delivery research through infrastructure that supports the identification, enrollment, and retention of ethnic and racial minority cancer patients being treated in academic and community oncology settings. Infrastructure that supports the recruitment and retention of racial and ethnic minorities is necessary, but may not be sufficient to facilitate the enrollment of diverse populations in precision medicine research that is conducted through the NCORP. This is because precision medicine research may not be optimally described and designed to enhance informed decisions about enrollment. As PMI research is being developed, it is critical to be able to anticipate the rates at which individuals from diverse populations are likely to participate in studies. Recently, we demonstrated that African Americans are likely to consider potential benefits to themselves, family members, and their community as part of making a decision to participate in cancer genetics research. Yet, only 23% of African American respondents in a national sample of adults reported that it was very likely that they would donate personal health information and blood and/or tissue samples to a biobank. Concerns about exploitation, investigators' motives, and distrust of researchers were identified as being important to decisions about participating in cancer genetics research; distrust of researchers was associated with a significantly reduced likelihood of donating to a biobank. In addition, respondents who had greater positive expectations about participating in cancer genetics research and those who reported more participation facilitators relative to barriers were most likely to be willing to donate to a biobank. Even with positive expectations about study participation, the majority of African Americans may be unwilling to participate in research that: (1) was sponsored by the government to provide information about the health of African Americans, (2) participation involves answering a questionnaire and providing a cheek swab, (3) the data will be used for the current study and also may be shared with other researchers to conduct future studies, (4) participants would not receive any results. Overall, 31% of respondents reported that it was very or somewhat likely that they would participate in this type of study and 69% reported that it was very/somewhat unlikely or neutral that they would participate in the study. Compared to women, men had 1.78 increased likelihood of participating in a PMI study (95% CI=1.06, 2.98, p=0.03). No other sociodemographic factors had a significant association with the likelihood of participation. While respondents who were distrustful of researchers had a lower likelihood of participation compared to those who trusted investigators, this association was not statistically significant (OR=0.62, 95% CI=0.37, 1.04, p=0.07). Beliefs about positive expectations, concerns about privacy, and negative expectations about the impact of genetic research did not have significant associations with the likelihood of participation. These findings suggest that the way in which PMI research is described to potential subjects may be an important factor in participation decisions. The NCORP infrastructure can be used to determine the optimal ways to describe precision medicine studies to cancer patients by examining enrollment and retention rates across research that has different objectives, benefits, and participation requirements. Citation Format: Chanita Hughes Halbert. Conducting precision medicine research in the NCI Community Oncology Research Program. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr IA28.