This study demonstrates the potential of racial identity to moderate how gain and loss-framed messaging, as well as culturally-targeted messaging, can affect receptivity to preventive health screening. African–Americans (N = 132) who were noncompliant with recommended colorectal cancer (CRC) screening completed a measure of racial identity centrality—encompassing the extent to which racial identity is a core component of self-concept—and then participated in an online education module about CRC screening, during which either gain or loss-framed messaging was introduced. Half of African–Americans were also exposed to a culturally-targeted self-help message about preventing CRC. Theory of Planned Behavior measures of attitudes, normative beliefs, perceived behavioral control, and intentions to obtain a CRC screen served as outcomes. Results confirmed that effects of messaging on receptivity to CRC screening depended on racial identity. Among low racial identity African Americans, gain-framed messaging most effectively increased normative beliefs about obtaining CRC screening, whereas among high racial identity African Americans loss-framed messaging was most compelling. However, these effects most strongly emerged when culturally-targeted self-help messaging was included. We discuss implications for health disparities theory and research, including a potential to simultaneously deploy culturally-targeted and tailored messaging based on racial identity.