Little progress has been made over the last 40 years to eliminate the racial/ethnic differences in incidence, morbidity, avoidable suffering, and mortality from cancer that result from factors beyond genetic differences. More effective strategies to promote equity in access and quality care are urgently needed because the changing demographics of the United States portend that this disparity will not only persist but significantly increase. Such suffering is avoidable. The authors posit that culture is a prime factor in the persistence of health disparities. However, this concept of culture is still poorly understood, inconsistently defined, and ineffectively used in practice and research. The role of culture in the causal pathway of disparities and the potential impact of culturally competent cancer care on improving cancer outcomes in ethnic minorities has, thus, been underestimated. In this article, the authors provide a comprehensive definition of culture and demonstrate how it can be used at each stage of the cancer care continuum to help reduce the unequal burden of cancer. The authors conclude with suggestions for clinical practice to eliminate the disconnection between evidence-based, quality, cancer care and its delivery to diverse population groups. CA Cancer J Clin 2010;60:12–39. © 2010 American Cancer Society, Inc.