Screening is available and effective in colorectal cancer (CRC) control, but underutilized. The purpose of this study was to use focus group data to develop recommendations for the development of educational interventions to increase CRC screening, using an audience segmentation strategy. Demographic segments were based on urban-rural residence, race (African-American, White) and sex. One hundred and sixty-five participants age 50+, with no history of CRC participated in 17 focus groups in Alabama urban and rural communities. Transcripts were examined by independent coders. Knowledge among participants was limited regarding age to begin screening, insurance coverage and risk factors for CRC. Perceived barriers to screening included lack of physician recommendation, cost/lack of insurance coverage, pain/discomfort and embarrassment. African-American men reported postponement in seeing their physicians. White women were proactive at initiating discussion of CRC screening with their providers while African-American women felt that providers should drive the process. No urban-rural differences were identified. This study identified cultural and gender characteristics and perceptions that can be used in the development of demographically segmented health communication interventions to increase CRC awareness and screening.