Histoplasmosis is a rare opportunistic fungal infection. It is commonly seen in immunocompromised individuals from endemic areas. Adrenal glands are frequently involved in the disseminated disease. Here, we present the case of a retropositive patient with constitutional symptoms, where whole-body positron emission tomography/CT scan revealed intense 18F-fludeoxyglucose uptake in bulky adrenal glands, and subsequent positron emission tomography-guided biopsy helped in establishing the diagnosis of adrenal histoplasmosis.