A 65-year-old man who had received radiation therapy for nasopharyngeal cancer (NPC) 3 years earlier presented with a 3-week history of right upper quadrant abdominal pain and a feeling of fullness. There had been no evidence of metastasis on his follow-up examinations. Computed tomography scan showed a huge complex cyst with septa in the right hepatic lobe, and we performed an extended right hepatectomy to relieve his symptoms. Pathological examination revealed a large hepatic cyst with malignant cells along the cyst wall. The cytokeratin stain and CK-14 stains were positive, indicating an undifferentiated squamous cell carcinoma (SCC). The final diagnosis of primary SCC of the liver was confirmed by the clinical pathological features and negative in situ hybridization of Epstein-Barr ribonucleic acids (EBERs). We used EBERs to determine whether the cystic tumor was a primary lesion or a metastatic lesion from the previous NPC.