BACKGROUND: The epidermal growth factor (EGF) system comprises four receptors, HER1-4, and several ligands, and is cyclically expressed in endometrium from healthy fertile women. Our aim is to identify differences in expression of the EGF system between endometriotic and normal endometrium. METHODS: We previously examined the EGF system in endometrial samples from healthy women (n = 14). Here we examine samples from endometrium (n = 23), endometriomas (n = 10) and peritoneal endometriosis (n = 9) from women with endometriosis (n = 23). mRNA expression of receptors and ligands from the EGF system was analyzed by real-time PCR, and proteins were localized by immunohistochemistry. RESULTS: Endometrial mRNA for HER1-3 was high compared with our previous findings in healthy endometrium, whereas HER4 and the ligands were unchanged. Endometriomas show lower expression of HER1-3 and no HER4 expression. Significant differences were demonstrated in late secretory phase for HER1 and HER2 and in the proliferative phase for HER3 compared to healthy women. Immunohistochemically, HER2 was identified in all samples, predominately in glands and surface epithelium. In a few glands, HER2 was in both cytoplasm and cell membrane. CONCLUSION: We report quantitative and qualitative differences in the EGF system in endometriotic eutopic endometrium compared to endometrium from healthy individuals.