Biopsy of a cardiac mass remains a difficult and risky procedure. Successful sampling of target tissue is hampered by continuous cardiac motion and blood flow. Because the surrounding tissues are vascular, complications can include hemorrhage, tamponade, arrhythmia, embolization, and death. Conventional imaging modalities are of limited utility in this dynamic environment. The present report describes the use of the instrumentation system originally designed for creation of direct portocaval shunts with intracardiac echocardiography imaging to perform core biopsies of cardiac and juxtacardiac masses in six patients. There were no hemorrhagic complications, and pathologic diagnoses were obtained in five of six cases.