There is an uncommon, enigmatic chronic appendicitis that shares histologic features with typical Crohn's disease (CD), but it presents as appendiceal disease. Although most reported patients remain disease free after appendectomy, a small group progresses to more generalized CD. The density of granulomas is said to separate those patients whose disease remains confined to the appendix from those patients in whom CD develops elsewhere. We reviewed 20 cases of appendicitis morphologically resembling CD and compared them with 16 transmurally inflamed appendices from patients with known CD to evaluate whether any histologic features differentiate between patients in whom recurrent CD will develop in the gut and those in whom it will not. Eleven patients with the primary disease had no granulomas. The remaining nine patients had granulomas, ranging from 0.2 to 28 per cross section. Appendices from patients known to have CD never had more than 10.5 granulomas per cross section. Follow-up in 15 patients with the primary appendiceal disease was from 5 weeks to 11.5 years (median, 30 mo). Thirteen patients remained disease free, but in two, CD developed elsewhere in the gut. One of these had no granulomas, whereas the other one had 21 per cross section. Therefore, according to the data from our study and from other studies, most cases of this Crohn's-like disease of the appendix are self-limited, but a few are not. Histologic features alone, including granuloma density, do not always predict the clinical outcome. Follow-up is necessary.