Context: Family caregivers play a vital role in managing the pain of hospice patients with cancer; however, caregivers' knowledge of pain management principles and experiences as pain managers vary widely. Differences in cultural values and access to resources suggest that rural and urban hospice family caregivers may differ with regard to their pain knowledge and experience, but this has not been empirically investigated. Objectives: We sought to determine if rural and urban hospice family caregivers differed in terms of their knowledge of cancer pain management principles and their experiences managing cancer pain. Methods: Our study consisted of a secondary analysis of baseline, cross-sectional data from hospice family caregivers (N = 196) participating in an ongoing cluster randomized crossover pragmatic trial. We performed multivariable regression to model associations between caregivers' demographic characteristics and their scores on the Family Pain Questionnaire (FPQ), which included subscales measuring pain knowledge and experience. Results: When controlling for other demographic variables, rural caregivers' scores on the FPQ knowledge subscale were worse (P = 0.01) than their urban counterparts. FPQ experience subscale scores and FPQ total scores were not statistically significantly different between the two groups. Conclusion: Rural hospice family caregivers report greater pain knowledge deficits than urban hospice family caregivers, although the two groups report comparable pain management experiences. Additional research is needed to better explain observed differences.