We report the case of a previously healthy 32-year-old man who was seen with flulike symptoms, dyspnea, and chest pain. The diagnosis was pyopneumopericardium, and pericardial tap revealed 1.3 L of purulent material. Computed tomography of the chest demonstrated a calcified mass inferior to the carina. Urgent exploration through a right thoracotomy revealed that the mass was adherent to the esophagus and pericardium. The subcarinal mass was resected. Pathological study demonstrated granulomatous lymph nodes, which were likely due to histoplasmosis. This is among the first reports of granulomatous erosion into the pericardium causing pyopneumopericardium. The patient made a good recovery, and his case demonstrates the importance of early imaging and mediastinal exploration for pyopneumopericardium.