Primary endometrioid adenocarcinoma rarely occurs in the vagina. Occasionally, endometrioid adenocarcinoma has a microglandular pattern. Herein, a case of primary endometrioid adenocarcinoma of the vagina with a microglandular pattern arising from pre-existing endometriosis long after a hysterectomy, is described. A 57-year-old postmenopausal woman developed a vaginal discharge over one decade after undergoing a hysterectomy. Microscopic examination of the vaginal smear and a biopsy specimen demonstrated an atypical glandular proliferation composed of columnar cells with occasional intracytoplasmic mucin and bland nuclear morphology, showing microcysts and numerous neutrophils within and around cysts. Immunohistochemically, the neoplastic cells were diffusely positive for CK7, MUC1, ER, and PR, and focally positive for vimentin, CEA, CK5/6, p63, p16(INK4a), and p53. A portion of residual endometrioid adenocarcinoma was identified adjacent to foci of endometriosis in the vaginectomy specimen. The patient has done well without evidence of recurrent disease for 1 year after surgery. Pathologists are encouraged to be aware of the occurrence of endometrioid adenocarcinoma associated with endometriosis in the vaginal stump after hysterectomy, and microglandular morphology which might be a source of misinterpretation.