Cancer mortality rates for Aberdeen Area Indians exceed U.S. rates with lung cancer being the leading cause of cancer death. The Sioux Cancer Study, an ancillary study of the Strong Heart Study, investigated cancer and cancer risk factors among tribal members aged 45-74 in three Sioux tribes in North and South Dakota. An Indian-specific health risk appraisal was used to collect data and provide specific recommendations to participants. The high rates of smoking (56% for men and 48% for women) explain the high lung cancer mortality rates. Intensive smoking cessation and prevention programs will likely have the greatest impact in reducing preventable cancer deaths. More accessible cervical and breast cancer screening provided by female health care providers is needed to reduce preventable cancer deaths among Sioux women. Pap smear screening is an especially high priority since cervical cancer mortality is 4.4 times higher than U.S. rates, all races. Programs targeted to reduce obesity and excessive alcohol use will also likely reduce preventable cancer deaths associated with high rates of obesity, diabetes and binge drinking. Community-based cancer prevention and control programs tailored to the cancer risk factor profile of the community are the best strategy to reduce preventable cancer deaths in Indian communities.