OBJECTIVES. This study uses Indian Health Service inpatient data to estimate cancer incidence among American Indians and Alaska Natives. METHODS. Hospital discharge data for 1980 through 1987 were used to identify cases of cancer for 21 sites in women and 18 sites in men. Estimates of incidence were directly standardized to data from the Surveillance, Epidemiology, and End Results Program for the same time frame. RESULTS. Cancers of the gallbladder, kidney, stomach, and cervix show generally high rates among many American Indian and Alaska Native communities, and cancers of the liver and nasopharynx are high in Alaska. Of the relatively common cancers in Whites, American Indians and Alaska Natives experience lower rates for cancers of the breast, uterus, ovaries, prostate, lung, colon, rectum, and urinary bladder and for leukemia and melanoma. Variation among geographic areas and among tribal groups is observed for many important cancer sites. CONCLUSIONS. This study demonstrates significant variations of cancer rates among American Indians and Alaska Natives, with important implications for Indian Health Service cancer control programs. The study also supports the potential use of hospital discharge data for estimating chronic disease among diverse American Indian and Alaska Native communities.