At present the most frequent cause of cardiac tamponade is neoplasma. A case of a 32-year-old male with recurrent cardiac tamponade caused by pericardium mesothelioma is described. Despite advanced neoplastic process in the pericardium, pleura and mediastinum, neither radiologic examinations of the chest, echocardiography, nor repeated cytologic examination of the pericardial exudate, could establish the etiology of the tamponade. Only after a pericardial window had been performed was it possible to: 1) establish the diagnosis and introduce causal treatment; 2) prevent recurrence of the tamponade; 3) perform cytoreduction of the tumor. It seems that in cases of chronic exudative pericarditis of unknown cause it is proper to perform an early pericardial window as a diagnostic and therapeutic procedure.