BACKGROUND AND OBJECTIVES: Pulse granuloma (PG), or giant cell hyaline angiopathy, is an immune-mediated reaction often following the implantation of plant-derived food particles. PGs are primarily found in the oral cavity and gastrointestinal tract and may represent a histopathological pitfall, being mistaken for other granulomatous conditions or tumors. This study is the first to compare oral to extraoral PGs, aiming to clarify the "hyaline angiopathy" seen in PGs by developing a detailed histochemical and immunohistochemical profile of oral and colonic PGs. METHODS: A computer search of 135,972 surgical pathology cases was conducted. PG histopathological slides, along with demographic and clinical data, were reviewed. Stains including Congo red, Masson trichrome, PAS, and immunostains CD31, ERG, and D2-40 were applied. RESULTS: Sixteen cases (11 oral, 5 extraoral) were identified, ranging from 7 to 81 years of age. Oral PGs were linked to odontogenic cysts, while extraoral PGs were associated with intestinal inflammation and perforation. Angiolymphatic marker expression was limited to the inflamed connective tissue surrounding PG. CONCLUSIONS: Our findings suggest that PGs reflect a granulomatous response to edible components and support surgical excision. The absence of vascular markers indicates that the term "angiopathy" is misleading, proposing that these "wormy" structures are fibrocollagenous responses.