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A 64-year old Chinese male patient was admitted to our hospital because of severe jaundice that persisted for 2 months. No swollen lymph nodes or hepatosplenomegaly was detected on physical examination. His laboratory data indicated high levels of direct bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase. No abnormality was revealed on abdominal computed tomography (CT). However, positron emission tomography (PET)-CT revealed diffuse hypermetabolism in the liver and spleen. Ultimately, liver biopsy guided by PET-CT was performed, revealing that atypical lymphocytes diffusely infiltrated the liver. The immunohistochemical analysis demonstrated that the tumor cells were positive for CD20, Bcl-2, Bcl-6, MUM1, and c-Myc but negative for CD3, CD4, CD8, and CD10. Based on these findings, this patient was diagnosed with primary hepatosplenic diffuse large B-cell lymphoma. After the definite diagnosis, he received chemotherapy and remained in good health as of September 2019.