Myxoid leiomyosarcoma (mLMS) of the uterus is a rare neoplasm; thus, knowledge of its clinical behavior and morphology remains limited. We therefore reviewed 30 cases initially diagnosed as uterine mLMS to better characterize its clinicopathologic features. Diagnosis was confirmed in 25 subjects (average age 51.5 y), of whom 80% were stage 1 at presentation. The average tumor size was 10.8 cm. An infiltrative tumor border was observed microscopically in 24 cases (96%); the border in 1 case could not be assessed. Fourteen cases (56%) had >10 mitoses per 10 high-power fields, 8 (32%) had between 2 and 10, and 3 cases (12%) had <2 mitoses. Geographic tumor necrosis and moderate to severe nuclear pleomorphism were seen concurrently in 12 cases (48%). All tumors expressed smooth muscle markers. Estrogen receptor was expressed in 29.4% of cases. Eighteen of 21 cases (85.7%) were negative for ALK by immunohistochemistry. Follow-up information was available in 18 subjects: 8 died of disease, 6 were alive with local and/or distant recurrence, and 4 were alive with no evidence of disease. Individuals who died of disease tended to have tumors with >10 mitoses per 10 high-power fields. Among cases with ≥5-year follow-up, overall survival was 11.1%, significantly worse compared with reported survival rates for conventional LMS. The initial diagnosis of mLMS was revised in 5 cases. Four had a distinctive loose myxoid appearance, nuclei with vesicular chromatin, and ALK positivity by immunohistochemistry, suggesting, suggesting inflammatory myofibroblastic tumor. This diagnosis was confirmed by in situ hybridization in 2 cases. One additional myxoid tumor lacked smooth muscle or myofibroblastic features and could not be classified further. mLMS is an aggressive neoplasm characterized by infiltrative tumor borders and variability of other features (mitotic count, atypia, and necrosis). The differential diagnosis includes myxoid leiomyoma and inflammatory myofibroblastic tumor. Attention to distinguishing morphologic features and immunohistochemistry will aid in the interpretation. An illustrated algorithm with criteria for diagnosis is proposed.