Background: Chinese and Korean Americans have lower colorectal cancer (CRC) screening rates than other racial/ ethnic groups, which may be explained by a low level of CRC knowledge and a high level of misconceptions. This study explores the role of knowledge in CRC screening among these groups. Methods: Chinese (N=59) and Korean (N=61) Americans older than 50 were recruited from the Washington D.C. Metropolitan area. They completed a detailed survey and participated in focus groups to discuss their knowledge on CRC and CRC screening. Seventeen physicians, community leaders, and patient navigators participated in key informant interviews. Using a mixed methods approach, data were analyzed quantitatively and qualitatively. Results: Participants lacked knowledge about CRC and CRC screening. More than half did not know that screening begins at age 50 and there are several types of tests available. More than 30% thought CRC screening was not necessary if there were no symptoms or there was nothing they could do to prevent CRC. Focus group findings suggested understanding about CRC was limited by an inadequate source of linguistically and culturally relevant health information. For example, many participants considered CRC a western condition mainly caused by unhealthy diet. This led to under-estimations about their susceptibility to CRC. Knowledge was positively associated with self-reported screening. Participants who had higher knowledge scores were more likely to report ever having had a colonoscopy and confidence in ability to have CRC screening. Conclusions: Mixed-methods analysis provides multi-faceted perspectives on CRC knowledge and its influence on screening. Study findings can help inform interventions to increase CRC screening among Chinese and Korean Americans.