Extensive epithelial cell proliferation underlies the ductal morphogenesis of puberty that generates the mammary tree that will eventually fill the fat pad. This estrogen-dependent process is believed to be essentially dependent on locally produced growth factors that act in a paracrine fashion. EGF-like growth factor ligands, acting through EGF receptors are some of the principal promoters of pubertal ductal morphogenesis. Amphiregulin is the most abundant EGF-like growth factor in the pubertal mammary gland. Its gene is transcriptionally regulated by ERα, and recent evidence identifies it as a key mediator of the estrogen-driven epithelial cell proliferation of puberty: The pubertal deficiency in mammary gland ductal morphogenesis in ERα, amphiregulin, and EGFR knockout mice phenocopy each other. As a prognostic indicator in human breast cancer, amphiregulin indicates an outcome identical to that predicted by ERα presence. Despite this, a range of studies both on preneoplastic human breast tissue and on cell culture based models of breast cancer, suggest a possibly significant role for amphiregulin in driving human breast cancer progression. Here we summarise our current understanding of amphiregulin's contribution to mammary gland development and breast cancer progression.