We describe eight unusual uterine leiomyomas characterized by a component of cells that suggested skeletal muscle differentiation or resembled the rhabdoid cells of extrarenal rhabdoid tumors. All of the tumors were referred because of problems in differential diagnosis, particularly distinction from an epithelioid smooth muscle tumor, a smooth muscle tumor of uncertain malignant potential, or a tumor with skeletal muscle differentiation. The patients were aged 27 to 50 (mean, 38) years, and the presenting clinical features and gross appearance of the tumors were similar to those of typical uterine leiomyomas. On microscopic examination, seven of the tumors were well circumscribed, whereas one showed slight irregularity of its margin. The characteristic feature of the tumors was a variable number of rounded, polygonal, or strap-shaped cells with abundant deeply eosinophilic cytoplasm and fibrillar, or occasionally hyaline, intracytoplasmic globules. Cytoplasmic cross-striations were not identified. The cells usually had eccentric, round-to-oval nuclei with conspicuous nucleoli. A variable number of the rhabdoid/skeletal muscle-like cells, as well as cells without these features, contained multiple or multilobed, pleomorphic, hyperchromatic nuclei, thus qualifying the tumors as leiomyomas with bizarre nuclei. Foci of hydropic change were present in all of the tumors. The mitotic index was low (<1 mitotic figure/10 high-power fields) and necrosis was absent in all the tumors. The rhabdoid/skeletal muscle-like cells were immunoreactive for desmin and h-caldesmon, but not for cytokeratin (AE1/AE3) or skeletal muscle markers (myoglobin, Myo-D1, or myogenin). Intracytoplasmic whorls of intermediate filaments were observed in the cells of one case examined by electron microscopy; there was no ultrastructural evidence of skeletal muscle differentiation. The histologic, immunohistochemical, and ultrastructural features indicated that the peculiar cells in these leiomyomas likely represented smooth muscle cells with an unusual phenotype rather than the cells of uterine tumors with skeletal muscle differentiation, extrarenal rhabdoid tumors, or epithelioid smooth muscle tumors. An association with leiomyomas with bizarre nuclei also was suggested.