Abstract Pure mesenchymal tumors may occur anywhere in the female genital tract, but they are most common in the uterine corpus, leiomyoma being by far the most prevalent. These tumors, and other uncommon mesenchymal lesions within the uterine corpus and elsewhere in the female genital tract, may result in several diagnostic problems. Morphology remains paramount and, in most cases, an unequivocal diagnosis can be made based on examination of the hematoxylin and eosin stained sections, combined with an appreciation of the clinical and gross pathologic features. In difficult cases, immunohistochemistry can significantly contribute to the final diagnosis. In this article, the immunohistochemistry of neoplastic and nonneoplastic mesenchymal lesions of the female genital tract is discussed site by site, concentrating on markers that are of value in diagnosis and in differential diagnosis. The immunophenotype of mixed epithelial and mesenchymal neoplasms and pure epithelial neoplasms with a component of spindle cells is discussed, where appropriate, because these can enter into the differential diagnosis of a pure mesenchymal lesion.