Spindle cell epitheliomas of the vagina are rare benign tumors of uncertain histogenesis. It has been hypothesized that they originate from a pluripotent cell population. Here, we report 2 cases of spindle cell epitheliomas of the vagina. Both patients presented with a painless vaginal nodule. The resected lesions were solid, well circumscribed, and composed of a proliferation of epithelioid or epithelial cells admixed with spindle cells without atypia. The 2 cellular populations expressed epithelial and mesenchymal markers. Based on these morphologic and immunohistochemical findings, a diagnosis of spindle cell epithelioma was rendered in both cases. Furthermore, we describe for the first time the expression of WT-1 (Wilms' tumor protein 1) and calretinin in addition to the previously defined immunohistochemical profile.