Most breast cancer has a complex, multifactorial etiology. One consequence of this multifactorial phenomenon is that etiological heterogeneity may exist. This heterogeneity implies simply that two or more groups of breast cancer cases in the general population may have been caused by different sets of events. The ability to define etiologically heterogeneous subgroups in the population may facilitate a number of research and clinical issues. Studying etiologically homogeneous subgroups in the general population may improve the ability to identify etiologic agents. Identification of a homogeneous group of breast cancer cases may also aid breast cancer diagnosis or treatment, and may allow a more effectively application of cancer prevention and control strategies. Defining etiologic heterogeneity in the general population is one initial step in the process of understanding cancer etiology. Using knowledge such as that provided in the two examples presented here, formal case-control or cohort studies can be undertaken to examine whether the factors that define etiologic heterogeneity are involved in etiology. Furthermore, the results of studies of etiologic heterogeneity can point toward potential gene-gene or gene-environment interactions. The type of studies presented here can therefore serve a useful role in leading to more formal molecular epidemiological analyses.