Rationale: Nocardiosis is an uncommon and potentially life-threatening infection that usually affects immunocompromised hosts. No clinical guidelines have been established for managing this rare disease, and the optimal treatment modality remains unclear. Nocardia farcinica, a relatively infrequent pathogen of nocardiosis, causes a clinically aggressive infection. In addition to our patient data, our search of the literature for patients who presented with empyema caused by N. farcinica will provide fundamental information for optimal treatment modalities.Patient concerns: A 64-year-old man was diagnosed with empyema, 4 days following surgery for sigmoid colon cancer. Brain lesions were evaluated only after N. farcinica was isolated and identified as the causative pathogen through repeated culture tests.Diagnoses: N. farcinica was isolated from the pleural effusion and confirmed as the pathogen through 16S rRNA sequencing. Interventions:The patient was successfully treated with tube thoracotomy, neurosurgical evacuation, and a combination of trimethoprim/sulfamethoxazole plus imipenem. Long-term antibiotic therapy was required to prevent recurrence.Outcomes: Pyothorax showed a good clinical response to antimicrobial therapy and drainage of pleural effusion, whereas brain abscess did not respond to medical therapy and required surgery. The patient eventually recovered and continued chemotherapy as treatment for sigmoid colon cancer.Lessons: Although extremely rare, this report demonstrates the importance of considering Nocardia infection as the differential diagnosis in immunocompromised patients who present with empyema. In particular, because of the N. farcinica infection's tendency to spread and the resistance of the organism to antibiotics, aggressive evaluation of metastatic lesions and standardized support from microbiological laboratories are important. Surgery may be required in some patients with brain abscesses to improve the chance of survival.