Objectives. We examined behavioral trends associated with cancer risk and cancer screening use from 1997 through 2006 among American Indians/Alaska Natives (AI/ANs) in the Northern Plains region (North Dakota, South Dakota, Nebraska, and Iowa) of the United States. We also examined disparities between that population and non-Hispanic white (NHW) people in the Northern Plains and AI/ANs in other regions. Results. There was no statistically significant improvement among AI/ANs in the Northern Plains region for behaviors associated with cancer risk or cancer screening use, and there was a significant increase in the obesity rate. The prevalence of binge drinking, obesity, and smoking among AI/ANs in the Northern Plains was significantly higher than among NHW people in the same region and among AI/AN populations in other regions. Although the percentage of cancer screening use was similar for all three groups, the use of sigmoidoscopy/colonoscopy was significantly lower among the Northern Plains AI/ANs than among NHW people.Conclusion. These results indicate a need for increased efforts to close the gaps in cancer health disparities between AI/ANs and the general population. Future efforts should focus not only on individual-level changes, but also on system-level changes to build infrastructure to promote healthy living and to increase access to cancer screening.