Abstract While breast cancer incidence rates in Ohio are similar to US rates, mortality rates are 10% higher, with Ohio having the 5th highest breast cancer mortality rate in the US. Ohio has several underserved population groups including African-Americans and women living in Appalachian and rural counties. Using a place-based perspective, higher mortality rates were found in counties with higher proportions of African-American women, and in several Appalachian and rural counties. While biologic characteristics (e.g. triple negative disease) may explain the higher burden in urban counties with higher proportions of African-American women, other factors may be related to disparities among women living in Appalachian and rural counties. Higher proportions of late stage diagnoses were found in these two groups of counties. Prevalence of mammography in Ohio did not differ for black vs white women; however, women with lower levels of income and educational attainment were less likely to report a mammogram in the past 2 years, with lower prevalence in Appalachian and rural counties. Using a multi-level framework, based on a socio-ecologic model of disparities, reasons for disparities observed in Appalachian Ohio were examined. The multi-level model posits that the causes (and solutions) to disparities are not solely due to individual behavior but are caused by the interplay of factors from multiple levels of influence ranging from biology to policy. For the specific case of breast cancer disparities in Appalachia, using data from several sources, including ongoing research studies, a model was developed to explain, investigate and intervene on these disparities. At the biologic level, stress, related to socioeconomic conditions, contributes to more aggressive tumor characteristics and impacts individual risk factors such as smoking, obesity, alcohol and drug use. Lack of exercise and a higher prevalence of food deserts increase the prevalence of obesity. At the social relationship level, poor behaviors such as smoking, alcohol use and obesity are reinforced as a result of few role models for health promoting behaviors. The social and physical context contributes as access to mammography and treatment and genetic testing facilities, is challenging. Institutional level factors include poor quality mammography, lack of coverage for genetic testing and lack of quality treatment and screening services. Lastly, the social condition and policy level focuses on conditions in the region including lower economic resources and policies to assure screening, treatment and access to genetic testing services. Solutions to these problems encompass strategies at individual, social, institutional and policy levels including: transportation assistance, navigation, mobile mammography with outreach, telemedicine to improve genetic testing and treatment access, community and health care provider attention to modifiable behaviors such as diet/exercise, alcohol use and smoking, and legislation to assure quality screening, treatment and access to genetic testing. While some strategies are currently being implemented in Appalachia to address determinants of risk and access, more focus from the policy perspective must be directed toward reducing disparities related to place. Citation Format: Paskett ED. Place as a cause of breast cancer disparities in Appalachia [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES5-1.