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Hypereosinophilic syndrome (HES), which is characterized by eosinophilia in the peripheral blood, often causes various organ disorders, including those of the gastrointestinal (GI) tract. The eosinophils play a key role in inflammation in eosinophilic GI disorders (EGIDs), including HES with GI involvement. Here, we report a case of HES with GI involvement that showed major basic proteins (MBPs) deposition in the absence of marked eosinophilic infiltration in the mucosa of the GI tract. An 11-year-old boy presented with nausea and epigastric pain for one week. He had a history of idiopathic HES with eosinophilic cystitis, diagnosed at the age of 2 years. He had been taking a low dose of corticosteroids for 9 years. The peripheral blood eosinophil count was 2,254/渭L. Endoscopy revealed a swelling of the duodenal bulb mucosa. Histological findings of the duodenal mucosa revealed chronic inflammation, but no evidence of significant eosinophil infiltration and we could not diagnose him with HES with GI involvement or EGID. Immunofluorescent staining for MBP and galectin-10 was performed to detect intact and cytolytic eosinophils (eosinophil extracellular trap cell death: EETosis). Marked MBP deposition was evident in a small number of intact eosinophils in tissues from the duodenum, gastric antrum, and terminal ileum. The current case illustrates the utility of immunostaining for the detection of persistent eosinophilic inflammation, especially when cytolytic eosinophils are dominant.