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Oestradiol (E<jats:sub>2<\/jats:sub>) promotes CxCa development in <jats:italic>K14E7<\/jats:italic> transgenic mice expressing the HPV16 E7 oncoprotein under the control of the keratin (K14) promoter. E<jats:sub>2<\/jats:sub> mainly functions through oestrogen receptor \u03b1 (ER\u03b1). However, the role of ER\u03b1 in human CxCa has been underappreciated largely because it is not expressed in carcinoma cells. We have shown that deletion of <jats:italic>Esr1<\/jats:italic> (the ER\u03b1\u2010coding gene) in the cervical stroma of <jats:italic>K14E7<\/jats:italic> mice promotes regression of cervical intraepithelial neoplasia (CIN), the precursor lesion of CxCa. Here, we deleted <jats:italic>Esr1<\/jats:italic> in the cervical epithelium but not in the stroma. We found that E<jats:sub>2<\/jats:sub> induced cervical epithelial cell proliferation in epithelial ER\u03b1\u2010deficient mice. We also found that E<jats:sub>2<\/jats:sub> promoted the development of CIN and CxCa in epithelial ER\u03b1\u2010deficient <jats:italic>K14E7<\/jats:italic> mice and that all neoplastic epithelial cells were negative for ER\u03b1. In addition, proliferation indices were similar between ER\u03b1<jats:sup>\u2013<\/jats:sup> and ER\u03b1<jats:sup>+<\/jats:sup> CxCa. These results indicate that epithelial ER\u03b1 is not necessary for E<jats:sub>2<\/jats:sub>\u2010induced CIN and CxCa. Taking these findings together, we conclude that stromal ER\u03b1 rather than epithelial ER\u03b1 mediates oncogenic E<jats:sub>2<\/jats:sub> signalling in CxCa. Our results support stromal ER\u03b1 signalling as a therapeutic target for the disease. Copyright \u00a9 2018 Pathological Society of Great Britain and Ireland. 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