The diagnosis of malignant, uncertain malignant potential, and benign uterine smooth muscle tumors is derived from histologic criteria such as tumor cell necrosis, mitotic activity, and cytologic atypia. Morphologically, some variants of leiomyoma can be confused with leiomyosarcoma (LMS). In this study, we compared fascin expression in cases of leiomyoma, leiomyoma variants (LVs), uterine smooth muscle tumor of uncertain malignant potential (STUMP), and LMS, and sought to determine the potential role of fascin in differential diagnosis. Fascin expression was investigated through the immunohistochemistry of paraffin-embedded tissue in 79 cases of uterine smooth muscle tumor including 22 usual leiomyoma, 31 LV, 4 STUMP, and 22 LMS cases. The cases were scored on the basis of staining extent (from 0 to 4) and intensity (from 1 to 3), and were assigned a combined score. Fascin expression was present in 20 of 22 (90.9%) LMS, 2 of 4 (50%) STUMP, 1 of 31 (3.2%) LV, and 1 of 22 (4.5%) usual leiomyoma cases. There was a statistically significant difference in fascin extent and intensity between the LMS and benign groups, but no difference between the LMS and STUMP groups. The results of this study indicate that more distinct fascin expression exists in LMS than in the benign groups. Fascin can serve as a reliable immunohistochemical marker in distinguishing uterine LMS from LVs and usual leiomyoma, and it may usefully be used with histologic criteria in diagnosing problematic cases.