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Situs inversus (SI) is a rare congenital anomaly characterized by the transposition of thoracic and abdominal viscera. Laparoscopic pancreaticoduodenectomy (LPD) is increasingly used in patients with periampullar and pancreatic carcinomas. For patients with SI, LPD can be more complicated because of reversed anatomy and possible other associated anomalies that have not been expected before surgery.A female patient with SI totalis presented with inappetence, vomiting, and weight loss for 2 months. Imaging modalities and angiography revealed a mass in the periampullary region without obvious vascular abnormalities. The mass was successfully resected via LPD based on an elaborate preoperative plan. The surgical pathology report demonstrated adenocarcinoma of the duodenal papilla. The patient has been followed up for 4 months and no tumor recurrence or long-term complications were observed.LPD is technically difficult but feasible in patients with SI.