Background <p>Rural populations in the United States experience worse cancer outcomes than urban populations, yet less is known about whether rural–urban differences currently exist in cancer-related worries and beliefs. Prior research largely predates the COVID-19 pandemic, a period marked by healthcare disruption and declining trust in public health institutions.</p> Methods <p>We analyzed <i>n</i> = 9,301 U.S. adults (rural <i>n</i> = 1,234) participating in the Health Information National Trends Survey (HINTS) Round 5 Cycle 4 (2020) and Round 6 (2022). Multivariate regressions estimated associations between rurality and cancer-related worries, information overload, fatalistic beliefs, and perceptions of progress in cancer prevention and cure.</p> Results <p>Rural residents differed significantly from urban respondents in sociodemographic characteristics but reported largely similar levels of cancer worry, information overload, and fatalistic beliefs. In unadjusted models, rural residents had higher odds of perceiving themselves as likely to develop cancer and lower odds of reporting hopeful views of and perceived progress in cancer research. After adjustment, differences in perceived cancer risk were attenuated; however, rural residents continued to report significantly lower odds of high hopeful views about cancer progress and lower perceived progress in cancer research.</p> Conclusions <p>While most cancer-related worries and beliefs did not differ substantially between rural and urban adults, rural residents exhibited persistently lower optimism about cancer research progress, suggesting that rural–urban differences in cancer perceptions may reflect disparities in trust, visibility, or engagement with scientific advances. Targeted communication strategies emphasizing scientific progress may help address gaps in optimism among rural populations.</p>