Endometrial stromal sarcoma (ESS), uterine cellular leiomyoma (UCL), and uterine leiomyosarcoma (ULS) are composed mainly of spindle cells that express similar antigens such as desmin, smooth muscle actin (SMA), and muscle-specific actin (MSA). The differential diagnosis of an ESS versus a uterine smooth muscle tumor or an extrauterine spindle cell sarcoma can be problematic based solely on clinical presentation, histologic assessment, or routine immunohistochemistry. Recently, we reported that normal endometrium, but not myometrium, as well as five cases of ESS, were positive for CD10. We now report the results of CD10 immunohistochemistry in an additional 11 cases of ESS (total 16 cases), 10 cases of UCL, and nine cases of ULS. CD10 immunoreactivity was detected in 16 of 16 cases of ESS (100%) as compared to only 2 of 10 cases of UCL (20%) and none of nine cases of ULS (0%). We compared the utility of CD10 immunoreactivity with that of desmin, SMA, MSA, estrogen receptor (ER), and inhibin in these tumors. Although the majority of cases of UCL and ULS were positive for SMA, MSA, and desmin, a substantial portion of cases of ESS were also positive for SMA, MSA, and desmin. We conclude that in combination with SMA, MSA, and desmin, CD10 is a useful immunohistochemical marker in the differential diagnosis of ESS versus UCL or ULS.