Family history has taken on public health significance given its role in predicting a variety of chronic diseases common in adulthood, including breast cancer. Having a positive biological family history of breast cancer is generally associated with increased risk perception and mammography screening rates among first-degree relatives. Little is known, however, about the health beliefs and health practices of persons with unknown biological family history. In particular, middle-aged and older adults reared in adoptive families typically do not have access to current biological family history information without engagement in a birthparent search.Utilizing a sequential explanatory mixed-methods design, this study examined a breast cancer risk construction and risk management process among adult adoptees from a stress and coping perspective. Female adult adoptees over 40 years of age (N = 452) completed an online questionnaire that assessed vicarious experience, family history ambiguity, breast cancer risk perception, cancer worry, perceived control, perceived value of family history information, birthparent information-seeking, mammography compliance, and future screening intention. Structural equation modeling allowed the interplay of these 9 factors to be tested, and qualitative inquiry (N = 12) augmented quantitative findings by exploring aspects of risk perception development in greater depth. Quantitative results provide evidence that vicarious experience with breast cancer is a significant stressor that shapes perceived risk and motivates birthparent information-seeking, mammography compliance, and future screening intention. Qualitative results corroborate the importance of threat salience in risk estimation and suggest that adoptees further consider the impact of their lifestyle and screening behavior as either reducing or elevating their personal disease risk. Adoptees ability to exercise cognitive control and/or emotional regulation over the threat posed by family history ambiguity, the valence placed on family history as a risk factor, and the degree to which potential familial risks are internalized also contribute to the risk construction process.Reflections on health behavior theory are offered in light of integrated mixed-methods findings and study limitations. Implications for research and practice are provided. Emphasis is placed on adoptees as a special population worthy of further research and advocacy in the era of genomics-based medicine.