This monograph reports regional cancer mortality rates among American Indians and Alaska Natives (AI/ANs) within areas served by the U.S. Department of Health and Human Services (DHHS), Indian Health Service (IHS). These areas are comprised of certain counties found within 35 states. AI/ANs residing in these counties represent about 56% of the total AI/AN bridged single-race population in the United States. We present the cancer mortality rates for 1999-2003 for the principal cancer types and compare them with the general U.S. population rates during the same period. We also present the estimated IHS service population for each region. The purpose of this publication is to provide detailed information on the impact of cancer among AI/ANs, with a focus on the regional variability of cancer mortality for this population.