© 2015 American Cancer Society. BACKGROUND: Ethnic minorities, especially African Americans and Latinos, bear a disproportionate burden of colorectal cancer (CRC), as reflected in incidence, cancer stage, and mortality statistics. In all ethnic groups, first-degree relatives (FDRs) of CRC cases are at an elevated disease risk. However, underuse of CRC screening persists and is particularly evident among minority groups. The current study tested a stepped intervention to increase CRC screening among an ethnically diverse sample of FDRs of CRC cases. METHODS: A statewide cancer registry was used to recruit CRC cases and through them their FDRs. Relatives who were not current on CRC screening were randomized to intervention or usual-care control arms. The stepped intervention consisted of ethnically targeted and individually tailored print materials followed by telephone counseling for those unscreened at 6 months. RESULTS: The study sample of 1280 individuals consisted of 403 Latino, 284 African American, 242 Asian, and 351 white FDRs. Statistically significant effects were observed for the cumulative print plus telephone intervention at 12 months (26% in the intervention vs 18% in the control group) and the print intervention alone at 6 months (15% in the intervention vs 10% in the control group). The effect of the print intervention alone versus the cumulative interventions was not statistically significantly different. Stratified analyses indicated that the intervention was effective among white, Latino, and Asian individuals, but not among African-Americans. CONCLUSIONS: Overall, the intervention was effective in increasing screening rates. Oversampling racial/ethnic minorities allowed for the examination of effects within subgroups, revealing no effect among African American individuals. This finding illustrates the importance of including sufficient numbers of participants from diverse ethnic subgroups in intervention research to enable such stratified analyses. Cancer 2015;121:2951-2959.