This biennial American Cancer Society report reviews and provides the latest data on major modifiable cancer risk factors, preventative vaccinations, and use of cancer screening tests. Information is also provided on social, economic, and public policy factors that profoundly influence individual behaviors. The report is accompanied by the scientific paper “Updated Review of Major Cancer Risk Factors and Screening Test Use in the United States, with a Focus on Changes During the COVID-19 Pandemic,” published in Cancer Epidemiology, Biomarkers, and Prevention.