Colorectal cancer (CRC) is currently associated with one of the highest burdens of morbidity and mortality among American men and women. Racial/ethnic disparities are well documented and the subject of intense research and intervention. Our understanding of disparities related to awareness and perceptions about causes, risk factors, and screening for CRC among subgroups of blacks in the United States is limited. This may be in part because grouping US-born blacks and foreign-born blacks as one homogeneous group obscures possible within-group differences. This study aimed to explore the cultural perceptions of CRC among 3 ethnic subgroups of blacks: African Americans (US born), foreign-born blacks from English-speaking Caribbean countries, and Haitian-born blacks. The study was informed by a community-based participatory research approach, using a cross-sectional mixed qualitative and quantitative methods design. A total of 62 individuals from the 3 ethnic subgroups participated in semistructured, in-depth qualitative and structured quantitative interviews. Qualitative findings revealed no stark differences among the 3 ethnic subgroups in their overall perceptions of cancer as well as their attitudes related to barriers, motivation, and resources for CRC screening. However, there were subtle differences in perceptions of curability, preventive practices, and preferred sources of information among the three ethnic subgroups of US blacks. The study has important implications for the design of educational materials and targeted interventions for diverse groups of US blacks.