Estrogen (E) plays a pivotal regulatory role in the control of cell proliferation in the normal breast and breast cancer (BC). To identify genes with likely roles in proliferation control that are regulated by E and its downstream target c-myc, we compared transcript profiles of antiestrogens-arrested cells stimulated to reinitiate cell cycle progression by E treatment or c-myc induction. Approximately 2/3 of the probe sets significantly regulated by E (adjusted p < 0.01) increased in expression. Half of the E-regulated probe sets were also regulated by c-myc. Genes involved in cell growth, cell proliferation, and cell survival were over-represented in the E-regulated geneset. Analysis of selected candidates has identified a nucleolar protein whose expression is correlated with c-myc expression in BC cell lines. These data indicate that a significant component of E-induced mitogenesis is mediated by c-myc and that selected c-myc target genes may be surrogate markers of c-myc expression in BC.