The uterus and retroperitoneum have emerged as the most frequently reported anatomic sites of origin of perivascular epithelioid cell tumors (PEComas), a poorly defined neoplasm that is characterized by varying amounts of spindle and epithelioid cells with clear to eosinophilic cytoplasm that display immunoreactivity for melanocytic markers, most frequently HMB-45. Published reports on 41 previously reported uterine PEComas are reviewed in this report. Of these 41 cases, 31 originating in the corpus and for which there was adequate follow-up information (or clinical malignancy) were categorized into 2 groups: (1) a malignant group that was comprised of cases associated with patient death of disease and/or clinical malignancy as evidenced by local and/or distant extension outside of the uterus (n=13, group 1) and (2) a "nonmalignant" group of cases in which neither of the above features were present (n=18, group 2). Groups 1 and 2 did not significantly differ regarding duration of follow-up (25 mo vs. 24.3 mo, respectively, P=0.9) or patient age (45.61 y vs. 43.46 y, respectively, P=0.7). Five of the group 1 patients experienced distant (extra-abdominal) metastases. The group 1 tumors were significantly larger than the group 2 tumors (averages 9.6 cm vs. 4.67 cm respectively, P=0.04); however, there were no size thresholds that, in of themselves, reliably classified 75% or more of the cases in both groups. Coagulative necrosis was highly associated with group 1, being present in 82% of cases as compared with only 11.8% of group 2 cases (P=0.0002). Eighty-eight percent of the group 2 cases had a mitotic rate of <or=1/10 high power fields (HPF) as compared with 40% of group 1 cases (P=0.01). However, the absence of mitotic activity did not rule out malignancy, as 2 of the group 1 cases lacked mitotic activity and displayed metastases. Twenty-five percent, 49%, 56%, 73%, and 100% of tested cases displayed immunoreactivity for CD10, desmin, vimentin, smooth muscle actin, and caldesmon, respectively. PEComas are tumors of uncertain histogenesis and malignant potential that seem to display some morphologic and immunophenotypic overlap with smooth muscle neoplasia. A mitotic count of >1/10 HPF and/or coagulative necrosis are features that, if present, raise the definite potential for aggressive behavior.