Purpose: Tumors of the perivascular epithelial cell tumor (PEComa), first described in 1992, represent a rare soft tissue neoplasm of varying malignant potential. Cases of PEComa have been previously described in a few somatic and visceral sites, most notably in the gastrointestinal tract, genitourinary tract, and one extremity case in the thigh. To date, most malignant cases of PEComa have been resistant to chemotherapy, and as such, an appropriate therapy is not known. Case report: Here we describe the first case of PEComa of the upper extremity. Open biopsy revealed a high-grade malignant lesion, and the patient subsequently underwent both neoadjuvant therapy with doxorubicin, ifosfamide and mensa, and radiation therapy prior to wide surgical resection.After six cycles of chemotherapy, the tumor underwent an 80% reduction in size. Subsequent neoadjuvant radiation therapy of 5000 cGy did not further reduce the size of the tumor. Following limb sparing radical resection, pathology showed 20% necrosis within a high-grade malignant lesion. Twenty one months after beginning treatment, the patient shows no sign of local recurrence, but metastatic disease was confirmed after resection of a lung nodule. Conclusion: Given the favorable albeit partial response seen in this patient, the course of therapy outlined here may represent a good starting point for neoadjuvant treatment in a tumor with a historically bleak prognosis. In addition, the diagnosis of PEComa must now be entertained in the differential diagnosis of upper extremity soft tissue sarcoma.