The spread of metastatic cancer to the pericardium is the most common cause of cardiac tamponade in medical inpatient settings. Lung cancer, breast cancer, and the hematologic malignancies account for some three quarters of the cases. Occasionally, usually in lung cancer, the pericardial involvement is the first clinical presentation of the neoplastic disease. Differential diagnosis includes radiation pericarditis and cardiac toxicity from chemotherapeutic drugs, as well as any of the causes of pericardial disease in patients without neoplasm. Idiopathic nonneoplastic, noninflammatory pericardial effusion is surprisingly common in cancer patients. The initial cardiac tamponade may be managed with either needle tap or subxiphoid pericardiostomy. Pericardiocentesis, performed with echocardiographic guidance and followed by percutaneous catheter drainage for several days, is safe and effective in neoplastic pericardial effusion. It may be the only local therapy that is needed. Further local treatment, for those patients who develop recurrent cardiac tamponade after an initial drainage procedure, may include tetracycline sclerosis of the pericardial space, instillation of cancer chemotherapeutic agents, radiation therapy, and pericardiectomy. No controlled clinical trials of these methods of treatment are available. The choice of therapy is based on various considerations in individual patients, particularly the patient's general condition and the likelihood of a long-term response to treatment of the systemic neoplastic disease.