The true incidence of rectal cancer in HNPCC is still unknown. In our retrospective series analyzing 42 probands from HNPCC families, we found rectal cancer primaries in 29% of our probands. Patients with a first cancer diagnosed in the rectum developed metachronous colon cancer in 54% of the cases. These numbers indicate a requirement to discuss the most appropriate surgical procedure for preventive intervention (ileorectal anastomosis versus ileoanal pouch procedure).