Colorectal cancer (CRC) screening rates are comparatively low for U.S. Hispanics. To learn more about the factors influencing CRC screening among Hispanics living along the U.S.-Mexico border, 12 focus groups were conducted with Hispanic men and women aged 50 years and older in three Texas counties; Cameron County (Brownsville), Webb County (Laredo), and El Paso County, (El Paso). The focus group guide contained questions about health care behavior, knowledge about CRC, experiences with cancer, and factors that influence CRC screening. A total of 92 individuals participated with the majority aged 50-69 (75%). Twenty percent were born in the United States and 51% had lived in the United States for more than 20 years. Participants had low levels of education, income, and insurance coverage. The analysis revealed several overarching and contextual themes relating to knowledge, attitudes, beliefs, and emotions about cancer and CRC screening. A prevalent theme that emerged from all groups was frustration and a lack of confidence in the U.S. healthcare system. Few participants had been advised by their providers to obtain CRC screening. Lack of patient knowledge about colorectal cancer and screening appeared to be a critical factor influencing screening. Themes about death and pain due to cancer were prevalent as were cultural factors such as machismo and embarrassment. System level barriers such as cost, medical insurance and transportation also impacted screening. These findings suggest that strategies are needed to educate Hispanic residents of border communities about CRC and to motivate them to undergo CRC screening.