To study the role of mast cells in the differential diagnosis of cellular leiomyoma and endometrial stromal sarcoma of uterus and its mechanism.Using SP immunohistochemical technique, the expression of proliferating cell nuclear antigen (PCNA) and mast cells in 25 cellular leiomyoma (CL) and 26 endometrial stromal sarcoma (ESS) of uterus were examined. The expression of estrogen receptor (ER) and CD44v3 in cellular leiomyoma was also studied.The expression of PCNA was not significantly different from CL or ESS (P > 0.05), while mast cell count was statistically different between them (P < 0.01). Using a value of less than 7 mast cells per high power field was useful for the diagnosis of ESS, yielding 100% sensitivity and 92.0% specificity. There was a positive correlation between the mast cell count and CD44v3 in CL (r(s) = 0.589, P < 0.01), though no correlation was observed between mast cell count and PCNA or ER.Number of mast cells is valuable for the discrimination of CL from ESS in the uterus. The mechanism and the role of higher quantity of mast cells in CL need further study.