Positron emission computed tomography (PET)/CT is a common modality used in the workup of neoplastic conditions. However, false-positive results may be produced by underlying infectious processes. We report two cases of false-positive PET/CT studies secondary to histoplasmosis infections in both a pediatric and a young adult patient. After the diagnoses, one patient was observed with no therapy and the other received a complete course of itraconazole. In both cases biopsy results were positive for fungal elements consistent with histoplasmosis. Both patients were successfully managed and have had follow-up histoplasmosis titers that reveal resolving infections.