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BACKGROUND: Isolated malignant pericardial effusion is a manifestation of primary cardiac lymphoma (PCL) and primary effusion lymphoma (PEL), rare types of non-Hodgkin's lymphoma (NHL). The diagnosis is based on different cytological methods and analyses including DNA-image cytometry (ICM-DNA). DNA-aneuploidy has been reported to be highly specific for malignancy. CASE DESCRIPTIONS AND RESULTS: A 75-year-old man and a 66-year-old woman underwent urgent pericardiocentesis for cardiac tamponade due to large pericardial effusion. In both patients pericardial fluid analysis showed highly atypical blastic lymphoid cells expressing CD45 (both patients) and CD20 (assessed only in one patient), and ICM-DNA revealed significant DNA-aneuploidy (2c deviation index 9.22 and 10.73 respectively, 75% and 60% respectively of the target nuclei in aneuploid areas). Extensive staging examinations did not identify any other tumour manifestation. Although in neither of the two patients systemic chemotherapy was administered, both were free of cancer after a follow-up of ten and nine years respectively. CONCLUSIONS: Despite the highly atypical cytomorphology including unequivocal DNA aneuploidy, long-term survival in both patients strongly suggests that pronounced reactive lymphocytic changes are probably due to viral pericarditis rather than PCL or PEL as underlying conditions. It seems that DNA-aneuploidy may be not absolutely specific for the detection of malignant lymphoid cells in pericardial fluid.