Estrogen receptor (ER)3 geneexpression in breast epithelium is an intricatelyregulated event. The human ER gene is transcribed fromat least three different promoters which are expressedin a cell- and tissue-specific manner, and result in mRNAisoforms with unique 5'-untranslated exons. The ER isoverexpressed in about two thirds of breast tumors, andeven in early premalignant breast lesions compared with adjacent normal breast epithelium.Furthermore, normal breast epithelium as well as breastcancer tissue contains alternatively spliced ER mRNAvariants where single or multiple exons are skipped. It is still unclear if any or all of the ERmRNA splicing variants are translated in vivo, and if achange in the balance of ER variants could effect tumordevelopment and progression to hormone-independent growth. Although infrequent in primary breastcancer, single amino acid changes within the ER inmetastatic disease which might influence cellproliferation may also contribute to neoplasticprogression of the mammary epithelium.