Fatalistic beliefs about cancer prevention can be a significant deterrent to one's likelihood of engaging in cancer prevention behaviors. Lower education and less access to cancer information among rural residents may influence their level of cancer fatalism. The purpose of this study was to examine rural-urban differences in fatalistic beliefs about cancer prevention and cancer information sources using data from the 2007 Health Information National Trends Survey (n = 1,482 rural and 6,192 urban residents). Results showed that rural residents were more likely to endorse multiple fatalistic beliefs about cancer prevention than urban residents even after controlling for other significant demographic correlates. Urban residents were more likely to use the internet as their primary cancer information source, whereas rural residents were more likely to rely on print material and healthcare providers. Future educational work to communicate relevant and accurate cancer prevention information to rural residents should consider not only information access but also rural culture and fatalistic perspectives.