Introduction: Blastocystis hominis is a single-celled organism that is usually found in the intestinal tract. Clinical manifestations of B. hominis infection in humans are nonspecific and include diarrhea, abdominal pain, cramps or discomfort, and nausea. Case description: A 47-year-old male came with a chief complaint of worsened shortness of breath for 2 weeks before being admitted to the hospital. Chest ultrasound showed a large right pleural effusion. We performed thoracocentesis and inserted a chest tube to drain the pus. Lugol staining of the pleural fluid showed the presence of B. hominis. The patient was treated with metronidazole and trimethoprim/sulfamethoxazole (TMP/SMX). Discussion: B. hominis has an equivocal role among intestinal parasites due to a lack of knowledge regarding its biology and evidence of its pathogenicity. Based on this case, the treatment that we provided produced a good response for the patient, and B. hominis as the cause of the disease can be considered. Conclusion: Despite it being thought to only infect the intestinal tract, in this case, we found that B. hominis can also be the cause of thoracic empyema. Treatment with metronidazole and TMP/SMX in the patient resulted in the resolution of the disease.