BACKGROUND Our novel approach is a hybrid between transanal endoscopic microsurgery (TEM) and single-port laparoscopy that we have termed TransAnal Minimally Invasive Surgery (TAMIS). We report the clinical application of this technique and present preliminary data that show TAMIS to be an effective tool for resection of both malignant and benign lesions of the rectum. METHODS Over a 3-month period (May-July 2009) all patients with rectal lesions who were candidates for conventional transanal excision were offered the option to undergo TAMIS resection. Patients with biopsy-proven malignant lesions were required to undergo endorectal ultrasound preoperatively to determine tumor stage. To perform TAMIS, a single-incision laparoscopic surgery port (SILS Port, Covidien) is introduced into the anal canal by applying steady manual pressure. Once seated in position, endoscopic access to the rectal vault is gained and pneumorectum is established. With this access, ordinary laparoscopic instruments, including graspers, thermal energy devices, and needle drives, are used to perform the transanal excisions. RESULTS Six patients, aged 43-85 years old (mean = 59.8), underwent TAMIS resection of rectal lesions. The average distance from the anal verge was 9.3 cm and the mean tumor diameter confirmed by pathology measured 2.93 cm. There were no conversions from TAMIS to conventional transanal excision. While the average operating time was 86 min, four of the six TAMIS resections (67%) were completed in less than 1 h. The mean set-up time was only 1.9 min and this may be one reason that the mean operative time was considerably less than the average operative time for TEM surgery (120-140 min). In short-term follow-up, there was no morbidity or mortality observed. CONCLUSIONS TAMIS is a feasible alternative to TEM, providing its benefits at a fraction of the cost.