Objective To investigate the expression and clinicopathological features of fumarate hydratase (FH) in multiple leiomyoma of the uterus. Methods Relevant clinicopathological data of patients with multiple leiomyoma of the uterus diagnosed pathologically between September 1, 2018 and August 31, 2019 were collected from the Department of Pathology of West China Second University Hospital. The morphology, FH protein expression and prognosis of FH negative patients were observed. Results A total of 900 patients were included. Among them, there were 825 cases of nonatypical leiomyomas, 36 cases of leiomyoma with bizarre nuclei, 34 cases of cellular leiomyoma and 5 cases of mitotically active leiomyoma. A total of 69 patients with negative FH expression were included, with an average age of (37.28±8.22) years. Among them, there were 43 cases of nonatypical leiomyomas, 19 cases of leiomyoma with bizarre nuclei, 6 cases of cellular leiomyoma, and 1 cases of mitotically active leiomyoma. At low magnification, staghorn shaped blood vessels, alveolar pattern edema, palisade distribution of smooth muscle cells and bizarre nuclei smooth muscle cells could be seen in patients with negative FH expression. At high magnification, cytoplasmic eosinophilicglobules andeosinophilic nucleolus surrounded by a halo could be seen in patients with negative FH expression. Among the 69 cases with negative FH expression, 60 cases (86.96%, 60/69) were followed up. All patients survived, of which 24 cases (40%, 24/60) recurred. Conclusion Immunohistochemically, the marker FH for multiple leiomyoma of the uterus is helpful to improve the identification of FH deficient leiomyoma in clinical work as well as early diagnosis in hereditary leiomyomatosis renal cell cancer syndrome.