Skene's (periurethral) gland carcinoma is a rare neoplasm accounting for less than 0.003% of all genital tract malignancies in females. Generally, adenocarcinomas of the female urethra are assumed to arise from the periurethral glands, the female homologue of the prostate. A case of Skene's gland adenocarcinoma without mucosal urethral involvement is presented. The histologic features of this tumor closely resembled those of prostatic adenocarcinoma. In contrast, clear cell and columnar/mucinous variants of female urethral adenocarcinomas have been described previously. Perhaps this signifies different biologic processes in the development of Skene's/periurethral and urethral adenocarcinomas in females. Additionally, we performed immunohistochemical staining that was reactive for prostate-specific antigen (PSA). Preoperatively, the serum level of PSA was increased and promptly decreased after surgical excision of the lesion. Therefore, preoperative and postoperative monitoring of serum PSA titers in patients with adenocarcinomas of the female urethra or periurethral glands (or both) should be considered.