We report our experience with two patients with myoepithelial carcinoma (MEC) of the extremity. An 83-year-old male and a 35-year-old female were treated with standard isolated limb infusion (ILI), using melphalan and dactinomycin. The first patient had a complete response (CR) that was sustained for two and a half years, until he developed a regional lymph node metastasis. The second patient had a 4.7 cm tumor located on her left hand with metastasis to the ipsilateral axillary lymph nodes. Initial treatment consisted of ILI and left axillary lymphadenectomy. The primary tumor regressed and showed signs of central necrosis, measuring 2.8 cm after 1 month. Though she was continuing to respond, a decision was made by her orthopedic surgeon to administer neoadjuvant radiation followed by surgical resection. J. Surg. Oncol. 2015; 112:510–513. © 2015 Wiley Periodicals, Inc.