A 41-year-old female with a history of total ulcerative colitis for 15 years is presented. After eight years, she was enrolled in a colonoscopic surveillance program with regular examinations every second year and with biopsy sampling for histologic assessment of dysplasia as well as for flow cytometric analysis. Neither dysplasia nor DNA aneupoloidy developed during the course of the follow-up, but, after seven years, the patient developed a rapidly growing malignant stricture in the lower rectum. At the time of diagnosis, a local gluteal metastasis was found. Following preoperative radiation therapy, laparotomy disclosed a rectal cancer with local growth in the pelvis. Despite an attempt to perform curative surgery, the patient deteriorated and died within four months after the diagnosis. The carcinoma was of a poorly differentiated, mucinous, signet ring cell type, and DNA analyses of both the tumor and its metastases were diploid. Retrospective analyses of mucin content in colonoscopic biopsies showed a gradual shift from sulfated mucin to sialomucin. This case underlines the fact that even rigorous follow-ups offer no absolute guarantee against incurable malignancy in surveillance programs for ulcerative colitis despite the inclusion of DNA analyses.