BACKGROUND Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is one of the treatment options in low-grade appendiceal mucinous neoplasm with peritoneal dissemination. The minimal invasive surgery approach was introduced to the field after years of traditional open technique. Multi-port laparoscopic and robotic techniques were reported with good short-term outcomes in very selected patients with low PCI scores. We describe here the first single-port laparoscopic approach of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. CASE REPORT We present a case of low-grade appendiceal mucinous neoplasm with peritoneal dissemination, in which single-port laparoscopic approach of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was completed through a 5.5-cm incision. A 35-year-old man with no medical illness underwent laparoscopic appendectomy for acute appendicitis 3 months earlier. Postoperative surgical pathology reported a low-grade appendiceal mucinous neoplasm with positive margin. After complete assessment and Tumor Board discussion, the patient was scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. A single gel port access was inserted through a 5.5-cm peri-umbilical incision. The Peritoneal Cancer Index score was 4, and the decision was made to proceed with partial cecectomy, omentectomy, peritonectomy, and hyperthermic intraperitoneal chemotherapy with the Sugarbaker mitomycin C-based regimen. Postoperative care was carried out following the Enhanced Recovery After Surgery protocol. The patient was discharged on day 3 without any complications. CONCLUSIONS A single-port laparoscopic approach in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is safe and feasible in very selected patients, and has the advantage of direct visualization and palpation through the incision to determine more accurate Peritoneal Cancer Index assessment in comparison to other MIS approaches. Nevertheless, additional prospective studies are needed.