This study investigates the clinical and histopathological characteristics of endometriosis (E) and adenomyosis (A), focusing on the factors that contribute to their progression and malignant transformation. The research involved 243 patients with E/A or normal uterine tissue, analyzed using histochemical and immunohistochemical staining techniques. The study found that cytokeratin (CK) CK7+/CK20− expression was present in E foci, distinguishing them from digestive metastases. Neovascularization markers, such as CD34+, were increased in areas with malignant transformation of E or A. Proinflammatory cells, including CD3+ lymphocytes, BCD20+ lymphocytes, CD68+ macrophages, and tryptase+ mast cells, were abundant in cases associated with malignant transformation. Additionally, a significant increase in the cell division index (Ki67+) and the inactivation of tumor suppressor genes p53, B-cell lymphoma 2 (BCL-2), and phosphatase and tensin homolog (PTEN) were observed in areas with E/A-transformed malignancy. The study concludes that proinflammatory, vascular, and hormonal changes trigger the progression of E/A and the onset of cellular atypia and malignant transformation, exacerbating symptoms such as pelvic pain and vaginal bleeding. These findings suggest potential therapeutic targets for future research.This study investigates the clinical and histopathological characteristics of endometriosis (E) and adenomyosis (A), focusing on the factors that contribute to their progression and malignant transformation. The research involved 243 patients with E/A or normal uterine tissue, analyzed using histochemical and immunohistochemical staining techniques. The study found that cytokeratin (CK) CK7+/CK20− expression was present in E foci, distinguishing them from digestive metastases. Neovascularization markers, such as CD34+, were increased in areas with malignant transformation of E or A. Proinflammatory cells, including CD3+ lymphocytes, BCD20+ lymphocytes, CD68+ macrophages, and tryptase+ mast cells, were abundant in cases associated with malignant transformation. Additionally, a significant increase in the cell division index (Ki67+) and the inactivation of tumor suppressor genes p53, B-cell lymphoma 2 (BCL-2), and phosphatase and tensin homolog (PTEN) were observed in areas with E/A-transformed malignancy. The study concludes that proinflammatory, vascular, and hormonal changes trigger the progression of E/A and the onset of cellular atypia and malignant transformation, exacerbating symptoms such as pelvic pain and vaginal bleeding. These findings suggest potential therapeutic targets for future research.