Although certain histopathologic patterns of epithelial proliferative breast disease are well established as indicating an increased relative risk for the subsequent development of mammary carcinoma, the biologic characterization of these changes is not known. One evident histologic characteristic of epithelial hyperplasia is the partial or complete loss of normal cellular polarity. Nonerythroid spectrin (fodrin) is a structural protein whose function is related to maintenance of cellular polarity. By immunohistochemical analysis, normal breast luminal epithelia contain fodrin confined to a characteristic basolateral distribution. Proliferative breast disease of the common type partially loses this polarized distribution of fodrin; fodrin immunoreactivity is not limited to a basolateral location but is present around the cell membrane and is inconsistently present at luminal interfaces. Whether this change in distribution of fodrin is a permissive event in the development of proliferative disease or merely an associated finding is not known.