Tumors of the Bartholin gland are rare, comprising less than 5% of all vulvar malignancies. Treatment is largely based on that of vulvar and anal squamous cell carcinomas. A case of invasive, grade 4, poorly differentiated squamous cell carcinoma of the Bartholin gland is presented. Our patient, a 47-year-old woman, had a history significant for cervical intraepithelial neoplasia treated with conization, type 2 diabetes mellitus, and tobacco use. The course of treatment included preoperative radiotherapy plus 5-fluorouracil and cisplatin chemotherapy, followed by restaging and posterior exenteration in combination with vaginal reconstruction.