The Division of Cancer Epidemiology and Genomics (DCEG) at the National Cancer Institute (NCI) is an intramural research program that studies factors that influence the development of cancer in large populations. This includes studying both environmental and genetic factors that transmit risk, developing absolute risk models in different populations, and developing strategies for the early detection of cancer. The research portfolio of the Biostatistics Branch at DCEG/NCI will be described, emphasizing the close synergistic relationship between methodology, epidemiology, and public health. Exciting opportunities for statistical innovation will be presented. Finally, we will motivate some of the methodological challenges through the design of DCEG's longitudinal cohort focusing on integrating electronic medical records, serial biospecimen collection and questionnaires, and wearable devices in studying cancer incidence.