HER2-positive (HER2+) breast cancers (BrCs) contain approximately equal numbers of ERα+HER2+ and ERα−HER2+ cases. An enduring obstacle is the unclear cell lineage-related characteristics of these BrCs. Although ERα+HER2+ BrCs could lose ERα to become ERα−HER2+ BrCs, direct evidence is missing. To investigate ERα dependencies and their implications during BrC growth and metastasis, we generated ERαCreRFP-T mice that produce an RFP-marked ERα+ mammary gland epithelial cell (MGEC) lineage. RCAS virus-mediated expression of Erbb2, a rodent Her2 homolog, first produced comparable numbers of ERα+RFP+Erbb2+ and ERα−RFP−Erbb2+ MGECs. Early hyperplasia developed mostly from ERα+RFP+Erbb2+ cells and ERα−RFP−Erbb2+ cells in these lesions were rare. The subsequently developed ductal carcinomas in situ had 64% slow-proliferating ERα+RFP+Erbb2+ cells, 15% fast-proliferating ERα−RFP+Erbb2+ cells derived from ERα+RFP+Erbb2+ cells, and 20% fast-proliferating ERα−RFP−Erbb2+ cells. The advanced tumors had mostly ERα−RFP+Erbb2+ and ERα−RFP−Erbb2+ cells and only a very small population of ERα+RFP+Erbb2+ cells. In ERα−RFP+Erbb2+ cells, GATA3 and FoxA1 decreased expression and ERα promoter regions became methylated, consistent with the loss of ERα expression. Lung metastases consisted of mostly ERα−RFP+Erbb2+ cells, a few ERα−RFP−Erbb2+ cells, and no ERα+RFP+Erbb2+ cells. The high metastatic capacity of ERα−RFP+Erbb2+ cells was associated with ERK1/2 activation. These results show that the slow-proliferating, nonmetastatic ERα+RFP+Erbb2+ cells progressively lose ERα during tumorigenesis to become fast-proliferating, highly metastatic ERα−RFP+Erbb2+ cells. The ERα−Erbb2+ BrCs with an ERα+ origin are more aggressive than those ERα−Erbb2+ BrCs with an ERα− origin, and thus, they should be distinguished and treated differently in the future.