Purpose More than 66% of the 200,000 newly diagnosed annual breast cancers in the US occurs in women over 55 years. Treatment advances result in excellent survival, yet older breast cancer survivors with co-morbidity may live longer, but not better after cancer. Decline in physical function, increased social isolation, and diminished economic resources increase vulnerability among older women. Rural women represent an underserved population. The purpose is to examine associations between comorbidity and predictors of health status among older rural breast cancer survivors. Methods Baseline data of 331 BCS age 55-90 years enrolled in the Rural Breast Cancer Survivors Study. Four surveys were used for data collection. Self-reported prescription medications were used as proxy for co-morbidity. Bivariate tests of association and multivariable recursive partitioning techniques were used for analysis. Results Mean number of prescription medication categories reported was 3.68 (SD = 2.3; range = 0- 12). Common prescription categories were: anti-hormonal, anti-hypertensive, and cholesterol- reducing agents. 69% was overweight or obese. BMI >31 was significantly associated with both poorer physical and mental health. Multivariate analyses indicated predictors of physical health status were higher BMI, >2 comorbid conditions, adverse changes in economic lifestyle, and lower social support. Predictor of poor mental health was >3 comorbid conditions. Conclusions Assessing co-morbid conditions, mental health status, social support, and economic burden after breast cancer treatment may better inform cancer survivorship care and comprehensive geriatric assessment. © 2014 Azuero et al.