Classic CECs are organized for large observational human population studies in which groups of people with a set of characteristics or exposures are followed systematically and prospectively for the incidence of new cancers, cancer mortality, and/or cancer-related outcomes. This definition includes large cohorts of cancer patients in observational studies involving responses to therapies and short- and long-term health outcomes occurring after diagnosis. Throughout the last two decades, CEC-based studies have helped to better understand the complex etiology of cancer and have provided fundamental insights into key environmental, lifestyle, and genetic determinants of this disease. Findings from CECs are critical for risk prediction analyses and models. These findings may also serve as a basis for cancer control measures for groups and populations at risk. Evidence generated by CECs has also been useful in providing the basis for the design and testing of many preventive and therapeutic interventions. Large biorepositories established by CECs already support genomic and epigenetic studies, and are beginning to support proteomic and metabolomic studies. Further, CECs are essential to genome-wide association studies (GWAS) and replication and/or expansion of prior GWAS findings that have led and will lead to the identification of putative cancer susceptibility loci of low penetrance and high frequency, and will potentially lead to the identification of genes associated with prognosis and survival for a variety of cancers. As the genes present in these loci are identified and their functions are clarified, the prospective exposure data accumulated from CECs afford opportunities for in-depth analyses of gene-environment interactions, which will be critical for the design of public health interventions. NCI recognizes that CECs are valuable resources that benefit the entire cancer research community and, that in order to be successful as a population sciences research resource, CECs need to accrue large and varied population samples and continue to follow-up with study participants over an extended period of time.