A 72-year-old woman had a 20-mm supraampullary villoglandular adenoma with a focal carcinoma in situ. The neurological status of the patient did not allow any major surgical procedure. Therefore laser therapy was performed using the Nd:YAG laser. Six laser sessions were necessary to destroy the whole adenoma. After 30 months of follow-up, there was neither endoscopic nor histologic recurrence. The laser therapy should be therefore considered in treating large sessile duodenal villous adenoma occurring in inoperable patients. However, a repeated endoscopic surveillance must be performed.