In the United States, public health interventions to control infectious diseases, lower infant and maternal mortality, and improve basic sanitation have led to a substantial increase in life expectancy for American Indians and Alaska Natives (AI/ANs). During 1940-1995, average life expectancy among AI/ANs increased 39%, from 51 years in 1940 to 71 years in 1995; however, AI/ANs experienced a parallel increase in mortality rates for chronic diseases, including cancer, which is the second leading cause of death for AI/ANs nationally and the leading cause of death among Alaska Natives. A previous study examining cancer mortality rates during 1989-1993 documented lower cancer mortality rates for AI/ANs than for the overall U.S. population, with regional variation. To understand cancer mortality among AI/ANs subsequent to that period, the Indian Health Service (IHS) and CDC analyzed death certificate data provided by CDC's National Center for Health Statistics for deaths among AI/ANs in five U.S. geographic regions during 1994-1998. This report summarizes the results of that analysis, which indicate that cancer mortality rates among AI/ANs nationally were lower than cancer mortality rates for all U.S. racial/ethnic populations combined. Rates for AI/ANs varied by region, with the highest rates found in the Alaska and the Northern Plains regions. Plans or modifications for cancer prevention and treatment programs should account for regional variation, and programs to discourage smoking initiation, encourage tobacco cessation, and promote colorectal cancer screening among AI/ANs in the Alaska and the Northern Plains regions should be expanded.