Endometriosis is a chronic inflammatory pathology estrogen-dependent. It is a condition affecting 5%-10% of women of reproductive age worldwide. Recent evidence indicating an embryological origin of endometriosis has provided new insights into its pathogenesis and potential therapeutic approaches. In this study, we compared the immunohistochemical expression of extracellular matrix molecules involved in the interaction between epithelium and stroma in endometriotic lesions and normal endometrial tissue. A total of 41 cases were analyzed. We examined the immunohistochemical expression of chondroitin sulfate proteoglycan 4 (CSPG4), keratan sulfate, chondroitin sulfate (CS-56), hyaluronic acid, and heparan sulfate (HEP). Our results showed higher expression of CSPG4 and CS-56 in epithelial endometriosis samples compared with normal endometrial tissue, while HEP, keratan sulfate, and hyaluronic acid showed decreased expression in epithelial endometriosis samples relative to normal endometrial tissue. Additionally, endometriotic stroma exhibited more frequent low intensity of hyaluronic acid and HEP compared with normal endometrial stroma. Investigating the levels of these molecules in eutopic and ectopic endometrial tissues enables the identification of potential therapeutic targets, and the development of novel treatments aimed at disrupting the adhesive and invasive properties of endometriotic lesions.