Engaging traditionally disadvantaged populations in research can be difficult. In fact, much of the evidence about cancer screening, treatment, and communication has been from studies of more affluent, well-educated Whites. Yet, patients from minority communities and with lower education and income are at greater risk for getting cancer, having more advanced cancer at the time of diagnosis, and suffering from worse outcomes once treated. As a result, efforts to reduce cancer health disparities are largely needed. Communicating one’s family history of cancer with other family members may have important implications for cancer prevention and health promotion. Accordingly, we sought to test a communication intervention with women in a safety-net clinic to promote the collection of family history for cancer, to improve cancer screening and early detection. This case study addresses necessary steps to ensure effective engagement, recruitment, and participant follow-up over a 14-month study period. We discuss recruitment as well as ethical challenges encountered, and describe our approach to adapt and deal with arising issues. Critical and practical lessons learned during the implementation of the randomized controlled trial are also discussed.