Understanding the differences in the incidence and mortality rate between African Americans and whites with CRC remains a perplexing problem. There is clearly not any one factor that explains the observed differences. Clinicians are just beginning to understand the importance of tumor biology, genetics, and lifestyle risk factors in explaining differences in how CRCs present and how they behave. This holds true regardless of a patient's race, sex, or age. Whether these factors will add disproportionately to the understanding of racial differences in presentation and outcome remains to be seen. Certainly, issues surrounding screening for CRC remain important in understanding the advanced stage of presentation for African Americans. In particular, a better understanding is needed of who is being screened and who is not and why. For example, are higher-risk African Americans being screened and if not what are the reasons for this? Importantly, even if one were able to eliminate the differences in stage at presentation between African Americans and whites, a survival disadvantage, albeit a much smaller one, would likely persist. Clearly, there is a need to understand better why African Americans are not receiving recommended therapy at the same rate as whites. This becomes even more important as the life-prolonging options for treating both localized and metastatic colon cancer continue to multiply. Finally, the apparent greater disparity in outcome for African Americans who have stage II disease should be explored in more detail, because this could have an immediate impact on treatment recommendations. For example, a 23-gene signature was recently found to be predictive of recurrence among patients with Dukes B colon cancer . If this model is validated in further studies, one could look at whether African-American patients are more likely to have this predictive signature. The problem has been clearly defined: a higher incidence of and a higher mortality from CRC for African Americans than whites. The task now becomes to continue to understand the reasons for the disparities and ultimately to come up with workable solutions so that the amazing progress in CRC treatment benefits all groups in this country.