Crohn's disease (CD) is diagnosed from information obtained clinically, pathologically, and radiologically. One important pathologic finding is a granuloma, which is helpful when a positive diagnosis of CD will affect treatment. Whether the presence of a granuloma has any clinical implication is not clear. We conducted a retrospective study to determine whether a granuloma found on a biopsy sample is associated with disease severity, fistulizing or perianal disease, frequent relapses, and extraintestinal manifestations. Eighty-two patients were identified who had a biopsy or bowel resection for CD between 1990 and 1994 at a tertiary referral center; 21 (25.6%) had a granuloma. This group was compared with a group of 61 patients without a granuloma. Forty-five percent were male (n = 37), mean age at diagnosis was 42.6 years (median, 39.5 years), mean disease duration at presentation was 8.8 years (median, 4.8 years), and mean follow-up duration was 2 years (range, 1 day to 10.2 years). No significant differences were demonstrated between the two groups by the Fisher exact test with regard to fistulizing or perianal disease, oral aphthous ulcers, disease severity, axial or peripheral arthralgia, episcleritis, anterior uveitis, erythema nodosum, or pyoderma gangrenosum.