History and admission findings: A 73 year old woman presented with increasing dyspnoea caused by a large pericardial effusion. Investigations: Transthoracic echocardiography revealed a diastolically 35 mm broad pericardial effusion. Subxiphoidal drainage controlled by ultrasound delivered 350 ml of a haemorrhagic fluid that was submitted to pathology and microbiology examination. This was completed by serological and immunological tests and a specific extensive search for malignant diseases, i.e. computer tomograms of chest and abdomen, mammography, bronchoscopy, gastroscopy and coloscopy. All examinations were negative. However, nested PCR analysis of blood leucocytes and of pericardial effusion revealed the pericardial presence of Epstein-Barr virus (EBV), consistent with a localized pericardial EBV persistence or reactivation. Treatment and course: Follow-up showed a complete resolution of the pericardial effusion without the necessity of further specific treatment. Conclusions: Although EBV infection is common in the general population, cardiac involvement, in particular in the adult, is infrequent and usually takes an uncomplicated course. The present case report demonstrates a beginning pericardial tamponade due to localized pericardial EBV persistence or reactivation without detectable systemic EBV infection. In addition, the importance of molecular tests for diagnostic accuracy is highlighted.