BACKGROUND & AIMS Long-standing ulcerative colitis has long been recognized as a risk factor for colorectal cancer, but there is still no universal consensus on the optimal management of ulcerative colitis patients with low-grade dysplasia in flat mucosa. Some authorities favor prompt colectomy, whereas others recommend continued surveillance. The purpose of our study was to determine the frequency with which flat low-grade dysplasia in ulcerative colitis progresses to advanced neoplasia (high-grade dysplasia or colorectal cancer) and whether specific variables could predict such progression. METHODS We reviewed the medical histories, colonoscopic findings, and surgical and pathology reports of 46 patients with ulcerative colitis diagnosed with flat low-grade dysplasia on a surveillance colonoscopy. The rates of neoplastic progression, as well as the frequency of advanced neoplasia, were tabulated. We correlated progression with several clinical and colonoscopic variables: the number of biopsy samples positive for flat low-grade dysplasia, the duration and anatomic extent of disease, patient age, and medication use. RESULTS Among these 46 patients, there were 7 cases of colorectal cancer, 5 of which were stage II or higher. Unexpected advanced neoplasia occurred in 4 of 17 (23.5%) patients who underwent colectomy for flat low-grade dysplasia. On an actuarial basis, the rate of neoplastic progression was 53% at 5 years. No clinical features predicted progression to advanced neoplasia. Cancers, including 2 at advanced stages, developed despite frequent follow-up surveillance examinations. CONCLUSIONS A finding of flat low-grade dysplasia during ulcerative colitis surveillance is a strong predictor of progression to advanced neoplasia. Early colectomy should be recommended for such patients.