Rural Appalachia has significantly higher overall cancer mortality compared with national rates, and lack of cancer screening is believed to be one of the contributing factors. Reducing the cancer disparity in this region must include strategies to address suboptimal cancer screening practices by rural Appalachian primary care providers (PCPs). To identify and investigate barriers to recommending and/or performing cancer screening among rural Appalachian PCPs. A semistructured focus group research design was used to elicit perceived barriers to recommending and/or performing cancer screening from 36 rural Appalachian PCPs (in 5 groups), including physicians, nurse practitioners, and a physician assistant. Findings indicate that rural Appalachian PCPs may not be performing recommended cancer screenings for a number of reasons. Time constraints, conflicting guidelines, and perceptions that patients do not value prevention were reported barriers to cancer screening. The PCPs in this study expressed frustration in attempting to encourage cancer screening and cited patient factors such as socioeconomic status, Appalachian culture, and cancer fatalism as barriers to cancer screening. Rural Appalachian PCPs encounter various barriers, such as lack of time and multiple cancer screening guidelines, to incorporating cancer screening into their practice routine. The findings underscore the negative impact of some cultural factors on preventive care delivered by PCPs. Increased provider education is needed on how best to encourage cancer screening within a cultural context and should include clarification and understanding of current cancer screening guidelines.