In the adult human mammary gland, most of the luminal epithelial cells express keratin 19 (K19+). However, in some small ducts and terminal ductal lobular units where branching would be expected to occur during pregnancy, the pattern of expression of this keratin is heterogeneous. While the keratin 19 negative cells (K19-) appear to have a high proliferative potential in vitro and in vivo, they have a lower secretory activity than the K19+ cells as monitored by expression of secretory component in the resting breast or casein in the pregnant gland. That the K19- cells form a separate proliferative compartment in the luminal cell lineage is suggested by the fact that they are absent in the prepubertal breast and only appear at puberty associated with branching ducts, and newly formed lobules. Our observations are consistent with the hypothesis that the K19- luminal cell is less differentiated than and may be precursor to the K19+ luminal cell, which represents the fully differentiated phenotype able to produce milk in response to a hormonal stimulus.