Religion and spirituality may influence outcomes in cancer prevention and therapy and contribute to cancer disparities in deeply religious communities like the Appalachian region of the United States. Finding a method to bridge this division is essential to reduce cancer health disparities in this population. Religious beliefs may lead patients to seek less aggressive medical care, influence them to believe that the diagnosis of cancer is a mandate from God and cannot be managed by the healthcare system, ultimately compromising outcomes and contributing to disparities in healthcare in such communities. The significant role of religion and spirituality in decision making relevant to cancer care has been reinforced through clinical experience and conversations with Appalachian focus groups. The influence needs to be recognized, emphasized and handled appropriately by healthcare providers. Physicians in practice need to be able to relate to this dimension and work with local spiritual support systems to provide both a medical and spiritual prescription for the individual's journey through cancer care or prevention approaches.