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Biopsy of the heart has become a widely applied technique in circumstances such as detection of a transplant reject or histological diagnosis of masses. Biopsy is usually performed in the catheter laboratory (cath-lab) under fluoroscopic guidance. Echocardiography guidance is employed but as 'ancillary' comforting support to the cath-lab operator and for the early detection of complications. Until now, only a transesophageal approach has been used for guiding biopsy of intracardiac masses. Today, thanks to the current echocardiographic technology employing second harmonics, the definition of cardiac structures has consistently improved in the transthoracic approach, possibly allowing the full transthoracic procedure to be performed. We describe the biopsy of a large mass in the right ventricle, completely conducted without the help of fluoroscopy, and completed only under the help and guidance of transthoracic echocardiography.