Collagenous colitis (CC) and lymphocytic colitis (LC) are clinical syndromes characterized by the presence of chronic watery diarrhea, few or no endoscopic abnormalities and biopsies that typically show normal crypt architecture, increased mononuclear inflammation in the lamina propria, absence of neutrophils, and increased intraepithelial lymphocytes. Patients with CC also have a thickened subepithelial collagen layer. We have noted, anecdotally, that biopsy specimens from some patients with CC or LC contain certain histologic features, such as Paneth cell metaplasia (PM), that are normally seen in inflammatory bowel disease (IBD), or other types of healed colitis, and thus may cause diagnostic difficulty. Therefore, the purpose of this study was to evaluate the prevalence and significance of IBD-like morphologic features in colonic mucosal biopsies from patients with CC or LC. Five hundred thirty-one routinely processed hematoxylin and eosin-stained colonic mucosal biopsies from 150 patients with clinically, endoscopically, and histologically confirmed CC (79 patients, male/female ratio: 14/65, mean age: 60 yr) or LC (71 patients, male/female ratio: 13/58, mean age: 55 yr) were evaluated in a blinded fashion for a variety of histologic features, including active crypt inflammation (cryptitis +/- crypt abscess), surface ulceration, Paneth cell metaplasia, crypt architectural irregularity, number of intraepithelial lymphocytes, and thickness of the subepithelial collagen layer (CC only). The results were compared between CC and LC and correlated with the clinical and endoscopic data. None of the patients had or developed IBD during the study period. Active crypt inflammation was a common finding in both groups, seen in 24 of 79 CC patients (30%) and 27 of 71 LC patients (38%). Surface ulceration was not seen in any of the LC biopsies but was present in 2 of 79 (2.5%) CC patients. Paneth cell metaplasia was frequent in both groups and significantly more common in CC compared with LC patients. Forty-four percent of CC patients, but only 9 of 63 (14%) of LC patients had Paneth cell metaplasia (p <0.001). Crypt architectural irregularity, although rare, was present in 6 of 79 patients with CC (7.6%) and 3 of 71 (4.2%) patients with LC. In patients with CC, the presence of Paneth cell metaplasia was associated with more severe disease characterized by the presence of abdominal pain (p <0.001) and a higher frequency of bowel movements (>3 bowel movements/day) (p = 0.06). Also, active crypt inflammation correlated with antibiotic use at the time of clinical presentation (p = 0.04) and was present in the only two patients who had positive stool cultures (one each for and ). However, none of the other histologic findings correlated with any of the other clinical or endoscopic features, such as type of symptoms, stool consistency, type of medical treatment, associated autoimmune diseases or outcome (complete, partial, or no resolution) in either group of patients. Pathologists should be aware that some histologic features normally associated with IBD such as crypt irregularity and neutrophilic cryptitis and crypt abscesses are not uncommon in patients with CC or LC and that the presence of one or more of these features should not necessarily be interpreted as evidence against either of these diagnoses.