Cutis aplasia is a rare condition characterized by skin and subcutaneous tissue defects. Researchers have previously described both conservative and surgical management methods. We report herein the case of a neonate with extensive cutis aplasia involving 37% of the total body surface area. Due to the risk of meningitis and catastrophic hemorrhage associated with scalp defects, she underwent staged surgical procedures with skin harvesting and synthetic skin application, followed by the application of cultured epithelial autografts. This report highlights the challenges in temperature and fluid management as well as intraoperative positioning in a neonate with cutis aplasia.