Abstract The University of Guam (UOG)/University of Hawaii Cancer Center (UHCC) Partnership aims to build capacity to reduce cancer health disparities (CHD) of Pacific Islanders in Guam, Hawaii, and the US-associated Pacific Islands (USAPI) through cancer research, training, and outreach. It has been funded by sequential U56 and U54 grants from the NCI. At the core of the partnership activities are jointly conducted research products of regional relevance and global importance. Over the past period of U54 funding, six research projects were related to betel nut use exploring the associations of betel nut use and health related conditions and behaviors among users in Micronesia; sociocultural factors affecting betel nut chewing in Guam; the influence of betel nut use on the oral microbiome; the identification of alkaloids present in the varieties of betel nut on Guam; identification of salivary biomarkers in betel nut consumption; and the functional assessment of molecular components of betel nut involved in pro-inflammatory mechanisms of immune cells. Other research projects are addressing CHD-related research questions around cancer risk and risk perception: health information trends and needs in the Pacific among adults and youth; feasibility of electrical breast densitometry in assessing breast cancer risk; and breast cancer risk factors for Pacific Islander women. Collectively, over 60 manuscripts have been published, over 75 abstracts have been presented at national and international conferences, and at least 8 new grants have been awarded to members of the partnership. Since the Fall Semester 2009, 16 MS degree students at UOG have received fellowship support from the U54 grant, and two UOG graduates are enrolled in doctoral programs at US mainland institutions. Two students received an MS degree and two students received a PhD degree at UHCC with U54 fellowship support. One PhD graduate is now a faculty member at UOG and engaged in the partnership. Over the past six years, UOG developed a cancer health disparities curriculum tailored for the Pacific region, now a permanently sustained track in UOG's Micronesian Studies Program. In addition, mentorship and career development is provided to early stage investigators (ESI) at UOG: UHCC investigators have mentored 10 UOG ESI since 2009. Four UOG faculty received summer fellowships at UHCC; two subsequently secured pilot funding. Outreach projects are exploring community-based participatory approaches to youth tobacco use prevention and cessation in Guam, and the effectiveness of a social network-based approach to reducing tobacco-related cancer risk. Outreach activities have also contributed to the introduction and passage of significant public health legislation in Guam, resulting in decreased tobacco use and increased tobacco taxes, a percentage of which supports patient services in Guam as well as the Guam Cancer Registry. In conclusion, the unique multi-ethnic, sociocultural, and geographic characteristics of the UOG/UHCC partnership provide for many unique and important cancer research, training, and outreach opportunities with regional and global relevance. The Partnership has significantly increased research capacity at UOG and cultivated interest in cancer research among minority students attending the partner institutions. Outreach has resulted in model tobacco control policy in Guam. A regional research infrastructure has been established and resources have been leveraged to address Pacific Islander cancer health disparities in Guam, Hawaii, and the USAPI. Supported by NCI awards U54CA143727 and U54 CA143728. Citation Format: Hali R. Robinett, Rachael T. Leon Guerrero, Robert A. Underwood, Neal A. Palafox, David C. Ward, Carl-Wilhelm Vogel. University of Guam/University of Hawaii Cancer Center Partnership: Twelve years of progress in addressing cancer health disparities in Pacific Islanders. [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 A83.