Objective: Rare disease Background: In several studies, the presence of Howell-Jolly body-like inclusions within neutrophils has been observed in cases of HIV infection, SARS-CoV-2 infection, post-transplant immunosuppression, and during chemotherapy or antiviral therapy. The phenomenon of neutrophils exhibiting Howell-Jolly body-like inclusions on peripheral blood smears can be attributable to viral infections or the pharmacological effects of medications. Case Report: A 14-year-old male patient who had received a diagnosis of lymphoblastic leukemia a year ago underwent hematopoietic stem cell transplantation and was readmitted due to a recurrence of gastrointestinal graft-versus-host disease (GVHD). During treatment, tacrolimus was administered in conjunction with steroids to treat GVHD, yet the patient's diarrhea worsened. Examination of a peripheral blood smear revealed neutrophils, with cytoplasmic inclusions resembling Howell-Jolly bodies. Despite an increased dosage of tacrolimus, control of GVHD was suboptimal, and there was a risk of gastrointestinal infection. During further treatment, the patient developed symptoms of gastrointestinal bleeding, which, upon gastroscopy and colonoscopy, led to the diagnosis of extensive gastrointestinal mucormycosis. The therapeutic regimen was escalated to include oral amphotericin B, while continuing tacrolimus and discontinuing all other immunosuppressants. Conclusions: The present case highlights the presence of Howell-Jolly body-like inclusions within the cytoplasm of neutrophils observed in the peripheral blood smear of a patient after hematopoietic stem cell transplantation. Morphological analysis suggests that the emergence of these inclusions is highly likely to be induced by medications used in the treatment of GVHD.