Mast cells (MCs) have been reported in the myometrium and uterine smooth muscle tumors. We examined the number of MCs in various uterine smooth muscle tumors (including leiomyosarcomas) and assessed whether this feature might be of value in their pathologic diagnosis. The number of MCs in 95 uterine smooth muscle tumors, including 55 ordinary leiomyomas, 17 cellular leiomyomas, 8 bizarre leiomyomas, and 15 leiomyosarcomas, was counted using toluidine blue and immunohistochemical staining. The number of MCs that stained for tryptase was lowest in leiomyosarcoma and next lowest in ordinary leiomyoma; the number in each of these two groups was significantly lower than in the myometrium (p < 0.001). In cellular and bizarre leiomyomas, the number of MCs was significantly higher than in ordinary leiomyoma (p < 0.001 and p < 0.001, respectively) and leiomyosarcoma (p < 0.001 and p < 0.005, respectively). Statistical analysis revealed that counting the number of MCs and using a cut-off value of 16 MCs per high-power-field is useful for the differential diagnosis of leiomyosarcomas from cellular leiomyoma and bizarre leiomyoma, yielding 100% sensitivity and 96% specificity. The number of MCs was significantly lower in leiomyosarcomas at TNM stages III and IV than in those at stages I and II (p < 0.05), but there was no significant correlation between the number of MCs and patient survival. These results suggest that the number of MCs might be useful as part of a multivariate approach to the differential diagnosis of leiomyosarcoma from bizarre or cellular leiomyoma.