Primary effusion lymphoma (PEL) is a recently described subtype of malignant lymphoma which develops in association with human herpesvirus-8 (HHV-8) in human immunodeficiency virus (HIV)-infected patients. PEL presents predominantly as lymphomatous effusion in the body cavities without a definite mass or lymphadenopathy. The malignant cell has large-cell morphology with null immunophenotype and B-cell genotype. We describe an unusual case of HIV negative HHV-8 negative PEL patient. A 48-year-old man presented with symptoms of right lower chest pain and fatigue for 3 months. Chest radiography and CT scan showed right pleural effusion and pleural thickening and no evidence of lymphadenopathy. Examination of the pleural fluid revealed lympho-dominant exudate and the results of all cultures were negative. A malignant lymphoma of diffuse large B-cell type was confirmed by pleural biopsy. The results of serologic studies for HIV and PCR of HHV- 8 using pleura fluid and tissue were all negative.