We report 10 cases of a morphologically distinct vaginal polyp which has hitherto not been characterized. The polyps occurred in women aged 39 to 78 years (most were postmenopausal) and were from 1.0 to 3.0 cm. Most of whose location is known to us were in the upper vagina. Histologically, all the polyps were remarkably similar and composed of well-circumscribed expansile nests of epithelial cells embedded in a hypocellular fibrous stroma. The epithelial elements, which were morphologically bland, were predominantly glycogenated or nonglycogenated squamous in type but small tubules were present at the periphery of some of the nests in all cases. Some of the squamous nests exhibited central necrosis with or without calcification and, in 3 cases, some contained keratin pearls. In 3 cases, a few tubules unassociated with squamous elements were present. In 3 of 4 cases tested, the cells lining the tubules were positive with prostatic acid phosphatase and in 2 of 4 with prostate-specific antigen. The epithelial elements reacted with broad-spectrum cytokeratins and cytokeratin 7 but the mesenchymal component was negative. The squamous elements were estrogen receptor positive and the mesenchymal component estrogen and progesterone receptor positive. The histologic features of this polyp, which we term "tubulo-squamous polyp of the vagina," are constant and distinctive and differ from other polyps and from mixed tumor of the vagina. Several cases reported in the literature as vaginal mixed tumor or Brenner tumor are likely examples of this entity. Possible theories of histogenesis include a Mullerian origin, derivation from mesonephric remnants or derivation from urogenital sinus-derived epithelium. Positive staining in some cases with prostatic acid phosphatase and prostate-specific antigen raises the possibility of ectopic prostatic tissue, although the overall appearance is different from that entity, or derivation from paraurethral Skene glands, the female equivalent of prostatic glands in the male.