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Objective: Several minimally invasive techniques using natural orifices as an entrance site to the peritoneal cavity have been described recently. Pure natural orifice translumenal endoscopic surgery (NOTES) techniques have been mainly implemented to perform cholecystectomies and appendectomies, while more complex operations like colon resections have been described in a hybrid setting and with the use of the transumbilical approach. Here we describe the technique of transvaginal sigmoid colon resection for cancer with standard laparoscopy equipment., Materials and Methods: After developing the transvaginal technique of sigmoid colon resection in an experimental sheep model, we have performed this operation in a human patient for cancer. Twelve months of follow-up is reported., Results: A totally transvaginal R0 resection of the sigmoid colon for adenocarcinoma has been successfully performed in a female patient with laparoscopy equipment. The specimen included 13 lymph nodes, all of which were free of metastasis. Twelve months after surgery the patient is alive with no evidence of disease., Conclusion: A pure transvaginal NOTES approach to sigmoid colon cancer is feasible in human patients.