Columnar cell change (CCC) is common and has often been considered of little clinical interest. However, some investigators have suggested that it may be a marker for increased risk of breast cancer. To see whether CCC is subject to hormonal influences, the distribution of estrogen receptors (ER) was determined in a series of breast specimens showing this change. The cases came from 51 women age 35-80 years (mean 52 years) with the following associated findings: 27 carcinomas and 24 benign lesions. Consecutive sections were recut from the paraffin blocks: one was stained with hematoxylin-eosin and the other was immunostained for ER. Since CCC is the initial step in unfolding of lobules, a process which can evolve into various conditions, including cyst formation and epithelial hyperplasia, the distribution of ER was also evaluated in the latter conditions. In normal lobules, only a minority of epithelial cells were reactive for ER. In contrast, the cells showing columnar change uniformly expressed strong nuclear reactivity. In lobules undergoing unfolding with the formation of cysts, the lining epithelial cells remained positive even when they became cuboidal or flattened. The pattern of reactivity differs in the two types of hyperplasia. In hyperplasia of the usual type, the pattern was heterogeneous, with a majority of negative cells mixed with cells showing varying degrees of positivity. In columnar cell hyperplasia, the stratified epithelium maintained a strong uniform positivity. It is now recognized that columnar cell lesions include a wide spectrum of changes reaching a point at the upper end where the differential diagnosis is ductal carcinoma in situ. Other studies have shown that advanced CCC lesions with various degrees of hyperplasia and/or atypia are ER positive. The present findings indicate that, from the initial stage of the spectrum, the common columnar cells are strongly ER positive. Moreover, the observation that the lining cells in cysts are positive supports the theory that hormonal factors are involved in the development of fibrocystic changes.