<p class="a"><strong>Background:</strong> African Americans are disproportionately affected by colorectal cancer. Cancer fatalism is a construct that may be associated with poor participation in health-promoting behaviors, particularly colorectal cancer screening among African Americans.</p> <p class="a"><strong>Methods: </strong>This study explores the relationship among colorectal knowledge, cancer fatalism, and religious coping among 479 individuals attending African American churches in North Carolina. Linear regression analyses were performed with cancer fatalism as the dependent variable.</p> <p class="a"><strong>Results:</strong> Linear regression analyses showed that lower levels of colorectal cancer knowledge were significantly associated with greater levels of cancer fatalism. Negative religious coping was significantly associated with greater levels of cancer fatalism. No relationship occurred for positive religious coping or religious denominational affiliation and cancer fatalism. Lower education level and lower income level had an association with increased cancer fatalism.</p> <strong>Conclusions:</strong> Healthcare providers should educate African Americans about colorectal cancer. Also, healthcare providers and religious leaders should consider jointly developing strategies to reduce negative religious coping that is a phenol-<br /> menon rooted in strong social ties that thrive in religious settings, such as the African American church environment. Also, both education level and income level should be considered when developing interventions to address cancer fatalism among African Americans.<br />