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Background & Aims: Cultural, religious, and financial barriers can hinder uptake of colorectal cancer (CRC) screening in Arab communities. We aim to understand attitudes and barriers that contribute to the low rate of CRC screening among Palestinians in the West Bank., Methods: We performed a national, cross-sectional study of Palestinian adults older than 50 years. A self-administered questionnaire was developed and validated. Data were randomly collected in all major districts of the West Bank. The primary outcome was the willingness to undergo CRC screening. Multivariable logistic regression models were used to assess the strength of association between the primary outcome and its predictors while controlling for possible confounders., Results: Of 1601 people approached for an interview, 1352 agreed to participate (response rate, 84%). Only 193 had undergone CRC screening (14%); 1069 (79%) agreed to take a fecal occult blood test, 906 (67%) agreed to a colonoscopy examination, and 1098 (81%) were willing to undergo CRC screening if recommended by a physician. Only 194 (14%) said they had been informed about CRC screening by a physician. Urban residents were more likely to be screened for CRC than nonurban residents (odds ratio, 0.73; 95% confidence interval, 0.56-0.93; P = .011). Multivariable analysis showed that lack of education beyond elementary school or familiarity with CRC screening, distrust of Western medicine, religious objection, and finding the test to be embarrassing were all associated with decreased odds of accepting CRC screening., Conclusions: Based on a national, cross-sectional study of Palestinian adults, there are many cultural and religious barriers to CRC screening. Improving our understanding of these could increase screening among Arab populations in the Middle East and in Western countries., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)