A 53-year-old man from Hubei Province, China, was admitted to our hospital with a 1-month history of intermittent fever (highest temperature, >39 C), abdominal pain, diarrhea, fatigue, and weight loss associated with anorexia and cough. However, the patient had lived in Guangdong Province for a long period of time. Half a month before the patient's admission, an upper gastrointestinal (GI) endoscopy revealed chronic non-atrophic gastritis with erosion, fungal esophagitis, and xanthoma of the gastric corpus, without specific intervention. During the patient's hospital visit, a physical examination revealed the following: temperature, 37.8 C; pulse rate, 107/min; respiratory rate, 20/min; and blood pressure, 117/85 mmHg. The rest of the patient's physical examination results were unremarkable. Laboratory examinations showed low levels of hemoglobin (98 g/L), leukocytes (3.17 x 109/L), albumin (26.8 g/L), and prealbumin (0.062 g/L), increased levels of high-sensitivity C-reactive protein (78.44 mg/L), erythrocyte sedimentation rate (73 mm/h), neutrophils (76.1%), D-dimer (1.55 mg/L), and antinuclear antibody (1:100) and a positive result for the cytomegalovirus (CMV)-DNA (<4.00E+02 copies/ml). The patient's absolute neutrophil count was in the normal range (2.41 x 109/L). Electrolyte parameters were abnormal, with hyponatremia (129.0 mmol/L) and hypochloremia (88.8 mmol/L). Anti-HIV antibody was positive, and the patient's CD4 T count was 10 cells/mul, accounting for 2.16% of total T lymphocytes. The rest of the blood tests, including immunoglobulin, complement 3 (C3) and 4 (C4), hepatic transaminase, creatinine, extractable nuclear antigen, antineutrophil cytoplasmic antibody, and tuberculosis T-SPOT, were within the normal range. Alpha-fetoprotein, carcinoembryonic antigen, severe acute respiratory syndrome coronavirus 2 nucleic acid, and blood culture results were negative. Chest computed tomography (CT) revealed a thickened and blurred lung texture and multiple enlarged lymph nodes (abdominal, retroperitoneal, bilateral axillary, and supraclavicular). Abdominal ultrasound was non-contributory, except for gallbladder polypoid. A colonoscopy revealed multiple scattered and swollen ulcers in the ileocecal region and ascending, transverse, descending, and sigmoid colon, and multiple site biopsies were performed ( Figures 1A, B ). Ulcers were characterized by clear boundaries, with moss attached to the bottom of the erosions, and the largest ulcer (approximately 1.0 x 1.5 cm) was located in the transverse colon. The demarcation between the normal and flared areas was clear. Therefore, the patient was treated with cefixime, mesalazine, and ilaprazole for 1 week before the completion of colonic histopathology, but without clinical improvement. After 7 days, histopathological evaluation of the biopsies using hematoxylin and eosin staining revealed a chronic ulcer of the colonic mucosa with fungal granuloma and focal small abscess ( Figures 1C, D ). Next, biopsy tissues were specifically stained with periodic acid-Schiff (PAS) and Gomorrah's methylamine silver (GMS) stains. Briefly, the former involves staining with periodate followed by binding with Schiff's solution to reveal glycogen and polysaccharides in the tissue, whereas the latter involves the oxidation of periodic acid followed by the reaction of the aldehyde group with hexamine silver to expose metallic silver. PAS staining ( Figures 1E, F ) and GMS ( Figures 1G, H ) staining of the intestinal biopsy specimens were positive. Fungal spores with a transverse septum were observed in the tissue cells, which were presented in the form of short fusiform or sausage-shaped spores aggregated into mulberry shapes. Combined with the results of immunohistochemistry, cluster of differentiation (CD) 68(+), pan-cytokeratin(-), CD34(-), S100(-), and CMV(-) confirmed T. marneffei infection. Subsequently, the patient received antifungal therapy with intravenous fluconazole (400 mg once daily) and intravenous ganciclovir (250 mg twice daily) for 5 days, followed by oral fluconazole (200 mg once daily) for 9 days and ganciclovir (1,000 mg once daily) for 23 days. During hospitalization, the patient was continuously administered symptomatic treatment, such as mesalazine, amino acid, and alanyl-glutamine. A change in the antifungal treatment with fluconazole led to defervescence, and the patient's symptoms improved quickly. The patient was discharged from our hospital and maintained oral antifungal agents.