A rare case of pyothorax-associated large B-cell lymphoma occurring in Hong Kong is reported. The patient was a 64-year-old Chinese male who presented with shortness of breath and pleuritic pain. Radiological examination revealed left pleural thickening associated with bilateral pleural effusion. Open biopsy of the thickened parietal pleura revealed occasional large malignant lymphoid cells of B lineage admixed with fibrin and hyalinised fibrous tissue. These lymphoma cells were shown to harbour both Epstein-Barr virus and human herpesvirus type 8 by in situ hybridisation and immunohistochemical study, respectively. There was no associated lymphadenopathy and hepatosplenomegaly. The clinicoradiological presentation and pathological findings thus fulfilled the criteria of the so-called pyothorax-associated large B-cell lymphoma. Awareness of this rare entity, together with diligent histological examination and proper application of ancillary investigative techniques, are essential for making a correct diagnosis. The co-infection with Epstein-Barr virus and human herpesvirus type 8 in this case also suggests a possible pathogenetic relationship between pyothorax-associated large B-cell lymphoma and primary effusion lymphoma.