BACKGROUND: An examination of cancer incidence patterns in American Indians and Alaska Native (AI/AN) young adults may provide insight into their present and future cancer burden. METHODS: To reduce racial misclassification, incidence data were linked with the Indian Health Service (IHS) patient services database. Age-adjusted cancer incidence rates per 100,000 (AAR) and corresponding rate ratios (RR) for young adults (ages 20-44 years) were compared across IHS regions and for selected cancers within Contract Health Service Delivery Area counties by race (AI/AN vs non-Hispanic whites [NHW]) and sex. RESULTS: The all-sites cancer incidence rate was lower for AI/ANs (AAR of 83.8) than for NHWs (AAR of 111.2) (RR of 0.75) but varied by IHS regions. Among the leading cancers in AI/AN females the risk was elevated for stomach (RR of 3.22), colorectal (RR of 1.30), uterine (RR of 1.61), and kidney (RR of 1.39) cancers and was lower for breast (RR of 0.70) and thyroid (RR of 0.71) cancers. Among AI/AN young adult males the risk was elevated for stomach (RR of 2.62), liver (RR of 1.89), and kidney (RR of 1.59) cancers and lower for testicular germ cell cancer (RR of 0.64) and lymphoma (RR of 0.60). The risk for these and other cancers varied across IHS regions. CONCLUSIONS: Many of the cancer patterns that characterize the AI/AN population overall are apparent among young adults. Compared with NHW young adults, the overall cancer burden among AI/AN young adults was lower but varied for selected cancers and across IHS regions. Cancer control and research strategies are needed to address the unique genetic, social, cultural, and lifestyle aspects of AI/AN young adults.