Primary lymphomas of the heart are rare and frequently are diagnosed at autopsy. Modern imaging technology now permits early diagnosis and treatment. This report describes the clinical, histologic, immunophenotypic, and molecular genetic findings for 5 patients with malignant lymphoma restricted to the cardiac muscle, with or without pericardial involvement. All patients were women, with ages ranging from 40 to 68 years (median 55 y). The right atrium was involved in all cases with the left atrium, right ventricle, and pericardium affected in 1 case each. Clinical presentation included pericardial effusions associated with precordial pain, dyspnea, and bradycardia. Electrocardiographic changes included junctional rhythm, incomplete right bundle branch block and ST and T waves abnormalities, and ST segment elevation and first-degree atrioventricular block with intermittent complete heart block. In all cases, biopsy or resection of the lesion or cytologic examination of the pericardial fluid established a diagnosis. All tumors were of B-cell phenotype and included 4 cases of large cell lymphoma and one unclassifiable small cell lymphoma. In 2 cases, a follicular center cell origin was supported by reactivity of the neoplastic cells for CD10 and bcl-6 and by bcl-2 gene rearrangement by molecular analysis. One patient died shortly after diagnosis due to cerebral infarction. Two patients are alive without disease after chemotherapy with CHOP after 120 and 192 months. One patient underwent chemotherapy with CHOP and rituximab, and shows persistent cardiac involvement by lymphoma but with a decrease in tumor burden at 7 months of follow-up. One patient was lost to follow-up. Clinical outcome is variable; however, early diagnosis in conjunction with effective treatment (surgery and/or chemotherapy) may result in an excellent prognosis. Primary cardiac lymphoma should be included in the differential diagnosis of a right atrial mass.