Objectives Colorectal cancer (CRC) screening continues to be underused, particularly by Latinos. CRC and colonoscopy fear, worry, and fatalism have been identified as screening barriers in Latinos. The study purpose was to examine the relationship of optimism, fatalism, worry, and fear in the context of Latinos referred for CRC screening. Methods Our sample included 251 Latinos between the ages of 50 and 83 years who had no personal or immediate family history of CRC, no personal history of gastrointestinal disorder, no colonoscopy in the past 5 years, and received a referral for a colonoscopy. Face-to-face interviews were performed, and data were analyzed using regression models. Results Greater optimism ( β = −1.72, p < 0.000), lower fatalism ( β = 0.29, p < 0.01), and absence of family history of cancer ( β = 1, p < 0.01) were associated with decreased worry about the colonoscopy. Being female ( β = 0.85, p < 0.05) and born in the USA ( β = 1.1, p < 0.01) were associated with greater worry about colonoscopy and the possibility of having CRC. Family history of cancer ( β = 2.6, p < 0.01), female gender ( β = 2.9, p < 0.000), not following the doctor's advice ( β = 2.7, p < 0.01), and putting off medical problems ( β = 1.9, p < 0.05) were associated with greater fear. In the multiple regression model, lower optimism ( β = −0.09, p < 0.05), higher fatalism ( β = 0.28, p < 0.01), and female gender ( β = 0.9, p < 0.05) were associated with greater worry. Conclusions Interventions that address fatalism and promote optimistic beliefs may reduce worry among Latinos referred for colonoscopy. Interventions that alleviate colonoscopy fear because of family history of cancer particularly among Latino women may help improve distress about CRC screening. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]