Vaginal adenocarcinoma is the second most common primary cancer of the vagina, yet there has been very little study of most subtypes other than clear cell carcinoma. We reviewed 18 cases of primary vaginal endometrioid adenocarcinoma, in our experience the second most common subtype. The patients ranged from 45 to 81 years of age (mean 60). Most presented with vaginal bleeding, and had had a prior hysterectomy. Five had a history of unopposed estrogen therapy but none had a history of intrauterine diethylstilbestrol exposure. The tumors were at the vaginal apex in 10 cases, in the posterior wall in 3, the lateral wall in 3, and the anterior wall in 1. On microscopic examination, each of the tumors had a pure or predominant component of typical endometrioid adenocarcinoma. There was squamous metaplasia in 4 cases, mucinous metaplasia in 4, and prominent nonvillous papillae in 2. The tumors were grade 1 of 3 in 4 cases, grade 2 in 13, and grade 3 in 1. Eleven cases were FIGO stage I, 5 stage II, and 2 stage IV. Vaginal endometriosis was identified in 14 cases, and is important in indicating a primary vaginal tumor, rather than secondary spread from the endometrium. Other subtypes of adenocarcinoma (such as serous when the tumor has a papillary pattern) and atypical forms of endometriosis, including polypoid endometriosis, are the most common other differential diagnostic considerations. The prognosis seems to be good in low-stage patients, with 11 patients alive and well and 2 alive with recurrent disease.