It generally is believed that perikarya of ganglion cells in the human colorectum are confined to plexuses that lie deep to the mucosa, and that intramucosal perikarya are rare. We retrospectively reviewed 100 specimens from biopsies of normal and abnormal mucosa to further characterize intramucosal perikarya. The presence of intramucosal perikarya, their number, location, and grouping were recorded. Twenty-one specimens (21.0%) contained intramucosal perikarya. Intramucosal perikarya occurred throughout the colorectum in the muscularis mucosae or lamina propria and in normal mucosa, acute self-limited colitis, inflammatory bowel disease, cytomegalovirus-associated colitis, hyperplastic polyps, tubular adenomas, and high-grade intraepithelial neoplasia. In some specimens, intramucosal perikarya morphologically resembled microgranulomas or cytomegalovirus-infected cells. We demonstrated that intramucosal perikarya of ganglion cells are surprisingly common in normal and abnormal mucosa. Awareness of intramucosal perikarya is necessary to avoid confusion with microgranulomas or cytomegalovirus-infected cells.