Granular cell tumors (GCT) are infrequently found in the gastrointestinal tract (GIT), and only four previous reports have described lesions occurring simultaneously in different sites. The present case of 11 GCT, located in the esophagus, stomach, colon and pericolic adipose tissue, occurred in a 50-year-old Japanese woman. All GCT appeared histologically benign and there was no sign of recurrence at 3 years after surgery. Immunohistochemical analysis and comparison between this case of multifocal GCT and six cases of solitary benign GCT of the GIT, which were taken from the files of the Department of Pathology at Kitasato University (1986-2000), demonstrated the follow-ing: (1) all diffusely expressed S-100, DCC and bcl-2, and (2) median labeling indices for Ki-67, cyclin D1, p53 (Pab1801), and p21WAF1/CIP1 of 4%, 24%, 1% and 28%, respectively, for the multifocal tumors, and 3.5%, 23%, 1% and 29%, respectively, for the solitary lesions, with no significant difference between the two groups. Thus, the expression of cyclin D1 and p21WAF1/CIP1 may be involved in the tumorigenesis of both types of GCT. The present case emphasizes the need to evaluate the entire GIT when a single GCT is identified. Multifocal lesions should be treated conservatively by local excision because, as with the solitary tumors, they exhibit a benign biological behavior, consistent with their low Ki-67 immunoreactivity.