Fatty acid synthase is an enzyme that catalyzes the synthesis of long-chain fatty acids. The enzyme expression is minimal in adult tissues and very high in many cancers. Ulcerative colitis is a chronic inflammatory bowel disease that, when long-standing, is associated with an increased risk of colon cancer. The aim of the present study was to establish whether fatty acid synthase levels in the mucosa without dysplasia of patients with long-standing ulcerative colitis were higher than in control subjects. Three groups of patients were selected: 30 with active ulcerative colitis, 30 with ulcerative colitis in remission, and 30 undergoing colonoscopy for colorectal cancer screening, as healthy control subjects. Fatty acid synthase expression was evaluated with immunohistochemical procedures. The enzyme was detected in all patients with active colitis, in most patients with quiescent disease, in both pathologic and normal mucosa, but in only 3 healthy control subjects. Our results suggest that extension of ulcerative colitis is greater than that revealed by common diagnostic techniques.