We examined retrospectively 100 sigmoid colon resection specimens removed for diverticulitis (DD [diverticular disease]-diverticulitis), 53 adenocarcinoma specimens that also had diverticulosis (DD-adenocarcinoma), and 50 adenocarcinoma specimens that did not have DD (adenocarcinoma only) to study the mucosal changes that occur in DD. Documenting these histologic features could be helpful in deciphering changes seen in colonoscopic biopsy specimens from the sigmoid colon in older patients. Prominent mucosal folds were present in approximately 90% of all DD specimens. Increased mucosal lymphoplasmacytic inflammation at the bases of the prominent folds was present in 15% and 9% of DD-diverticulitis and DD-adenocarcinoma specimens, respectively. Eleven percent of the DD-diverticulitis and 4% of the DD-adenocarcinoma specimens had prolapselike mucosal abnormalities of the mucosa on the surface of the prominent mucosal folds. Mildly increased lymphoplasmacytic inflammation surrounded the diverticulosis ostia in approximately 25% of all DD specimens. All the diverticulitis ostia had neutrophilic and lymphoplasmacytic inflammation in the surrounding mucosa. No specimens had crypt distortion. Diverticular disease-related inflammation may be one cause of mild patchy inflammation that is occasionally observed in sigmoid colon biopsy specimens. Diverticular disease also should be considered as a cause of mucosal prolapse changes in sigmoid colon biopsy specimens. Other diseases should be considered when markedly increased mucosal inflammation, crypt distortion, or granulomas are present. Distinction between a DD-related incidental finding and a significant pathologic abnormality frequently can be made with the procurement of multiple biopsy specimens.