Idiopathic granulomatous appendicitis has been categorized as primary Crohn's disease of the appendix based on its pathologic features, although the clinical course of this condition simulates acute appendicitis. In this study we report the clinical and pathologic features of 10 cases of idiopathic granulomatous appendicitis and compare the histopathology to 14 appendices inflamed by Crohn's disease. The patients comprised six women and four men with an age range of 15 to 48 years (mean, 29 years). Six patients had acute onset of right lower quadrant abdominal pain while in three patients the presentation was subacute; one patient was asymptomatic. Focal neutrophilic infiltration of crypts with crypt abscesses, mucosal erosion and ulceration, fissures, transmural lymphoid aggregates, and mural fibrosis were comparable in idiopathic granulomatous appendicitis and Crohn's disease affecting the appendix. Fistulization occurred more commonly in Crohn's disease. Idiopathic granulomatous appendicitis contained 19.7 granulomas per tissue section (range, 2.75 to 71.0) compared with 0.3 granulomas per tissue section (range, 0 to 3.0) for appendices affected by Crohn's disease. No patient with granulomatous appendicitis treated by simple appendectomy had recurrence of disease at mean follow-up of 4.5 years. Our morphologic data support the clinical contention that idiopathic granulomatous appendicitis is nosologically distinct from Crohn's disease. Ironically, the presence of numerous granulomas is the histopathologic feature distinguishing idiopathic granulomatous appendicitis from Crohn's disease.