The development of molecular pathologic components in epidemiologic studies offers opportunities to relate etiologic factors to specific tumor types, which in turn may allow the development of better overall risk prediction and provide clues about mechanisms that mediate risk factors. In addition, this research may help identify or validate tissue biomarkers related to prognosis and prediction of treatment responses. In this mini review, we highlight specific considerations related to the incorporation of pathology in epidemiologic studies, using breast cancer research as a model. Issues related to ensuring the representativeness of cases for which research tissue is available and understanding limitations resulting from variable procedures for tissue collection, fixation, and processing are discussed. The growing importance of molecular pathology in clinical medicine has led to increased emphasis on optimized tissue preparation, which should enhance this type of research. In addition, the availability of new technologies including tissue microarrays, image scanning, and automated analysis to achieve high-throughput standardized assessment of immunohistochemical markers, and potentially other assays, is enabling consistent scoring of a growing list of markers in large studies. Concurrently, methodologic research to extend the range of assays that can be done on fixed tissues is expanding possibilities for molecular pathologic studies in epidemiologic research.