A 51-year-old male with AIDS (CD4 count 21 cells/μL) presented with chronic diarrhea, weight loss, and diffuse lymphadenopathy. Initial lymph node biopsy revealed granulomas with budding yeast, leading to a presumptive diagnosis of disseminated histoplasmosis. However, further molecular testing using panfungal PCR and sequencing identified *Talaromyces marneffei* (formerly *Penicillium marneffei*) from the lymph node. This case highlights the importance of advanced diagnostic methods in immunocompromised patients, as *Talaromyces marneffei* can mimic other fungal infections like histoplasmosis due to similar microscopic appearances, especially in endemic regions.
Key note: Molecular diagnostics are crucial for accurate identification of atypical fungal infections in immunocompromised patients, even when initial microscopy suggests common pathogens.