Since a definitive diagnosis of PEL rests on the presence of HHV-8 in the tumor cells, a lymphoproliferation of large immunoblastic, plasmacytoid and/or anaplastic cells, an immunophenotype of leucocyte common antigen CD45 positive, pan B-cell marker negative, and lymphocyte activated marker (CD 138, CD30, CD38, human leukocyte antigen DR and CD71) positive, it is essential for clinicians and pathologists to develop a high index of suspicion of PEL when handling HIV-positive patients with effusions without palpable tumor masses. The gene discussed is TNFRSF8; the disease is primary effusion lymphoma.