Appendiceal mucinous neoplasms are a rare and heterogeneous group of diseases with challenging clinical management decisions. They account for less than 1% of all cancers but their incidence is on the rise. Treatment is based on their stage and histology. Appendiceal neoplasms frequently metastasize inside the abdomen; this leads to tumor cell growth in the abdominal cavity, known as peritoneal carcinomatosis, and buildup of mucinous material, known as pseudomyxoma peritonei. While low-grade, early-stage tumors can be effectively treated with limited surgical resection, patients with low-grade, advanced-stage disease require peritoneal debulking and hyperthermic intraperitoneal chemotherapy. Therapeutic options for high-grade, advanced-stage mucinous tumors of the appendix have not been well established. Debulking surgery with hyperthermic intraperitoneal chemotherapy preceded and/or followed by systemic chemotherapy has been utilized based on some prospective but not randomized data. We present a case of mucinous adenocarcinoma of the appendix treated with neoadjuvant chemotherapy followed by cytoreductive surgery/hyperthermic intraperitoneal chemotherapy and adjuvant chemotherapy. Preoperative chemotherapy provided a favorable histologic response by converting initial mucinous appendiceal adenocarcinoma histology to a high-grade mucinous appendiceal neoplasm.