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This study describes a rare case of Human Immunodeficiency Virus and Human Herpes Virus 8 (HHV-8) negative primary effusion lymphoma (PEL)-like lymphoma in a patient with hepatitis B virus-related liver cirrhosis, diagnosed in a 66-year-old male who rapidly progressed to a sense of abdominal fullness. Cytological analysis of the pleural effusion demonstrated large atypical lymphoid cells with rounded nuclei, prominent nucleoli, and abundant cytoplasm. Immunocytochemistry of the pleural effusion detected atypical CD20 + lymphoid cells. The patient was hospitalized, and died following sepsis and multi-organ failure. Our case highlights that HHV-8-unrelated PEL-like lymphoma patients have different pathogenetic mechanisms of causality at the biological level, immunophenotype, clinical behavior, and prognosis.