Ulcerative colitis (UC) is generally considered an inflammatory disorder that always involves the rectum and may also involve more proximal portions of the colon, but always in a diffuse and continuous (non-segmental) fashion. Earlier biopsy studies have shown that both rectal sparing and patchy disease may occur during the natural history of UC and may, in fact, be accentuated by oral or enema therapy; but these features have never been evaluated in resection specimens. The purpose of this study was to evaluate the prevalence rates and degree of endoscopic and histologic patchiness of disease and rectal sparing in preoperative endoscopic biopsies and to compare the findings with those observed in colectomy specimens. In addition, we evaluated the effects of immunomodulators and anti-TNF-alpha therapy on normalization of mucosa. Cases of 56 UC patients, all of whom had at least 1 preoperative endoscopy with biopsies, and who subsequently underwent a colectomy for nonneoplastic complications, were collected and reviewed for a variety of inflammatory histologic features, such as patchiness of disease and rectal sparing. Both of these features were categorized as either absolute or relative according to predetermined criteria. All biopsies and resection specimens were graded for their inflammatory activity on a 5-point scale. An independent score was provided for each portion of the colon, and a mean colitis score of the entire colon was calculated by adding all inflammatory grades for each colonic segment and dividing this number by the number of segments. Endoscopic, biopsy, and resection specimen findings were correlated with each other and with clinical and demographic features, such as duration of colitis, extent of colitis, and types of medications used for at least 6 months before resection. Overall, the mean colitis score in biopsies was significantly lower than in resection specimens (2.7+/-0.9 vs. 3.2+/-0.8, P<0.01). Evidence of rectal sparing and patchy disease occurred in 32.1% and 30.4% of patients by endoscopy, and 30.4% and 25% of patients by analysis of biopsies. Only 3 patients (5.4%) showed rectal sparing, and all of these were considered "relative" after evaluation of the patients' colectomy specimens. Six (10.7%) showed patchiness of disease in the colon resection specimen, 4 of which were absolute. After evaluation of all of the patients' preresection biopsy specimens and colectomy specimens, none of the patients (0%) showed complete absence of rectal involvement (absolute rectal sparing) after all of the tissue sections were evaluated. A significant correlation was noted between endoscopic and biopsy findings and between biopsy and colectomy findings, but poor correlation was noted between the patients' endoscopic features and the pathologic features in the patients' colectomy specimens. No correlation was noted between any specific type or combination of medication use and the presence or frequency of rectal sparing or patchiness of disease. These data indicate that absolute rectal sparing does not occur in UC patients even after long-term use of antiinflammatory medications. The presence of 1 (or more) tissue sections from an IBD patient's colectomy specimen showing complete absence of histologic features of chronicity or activity, but bordered on both sides by chronic or chronic active disease, should not represent a reason to change the patient's diagnosis from UC to Crohn disease.