Few cases of pulmonary embolism detected by transthoracic echocardiography (TTE) have been reported. We present a case of a patient affected by pulmonary embolism caused by protein C deficiency. Transthoracic echocardiography showed a thrombus in transit (ie, visualization of a thrombus within the pulmonary artery). A hypercoagulable state caused by deficiency of protein C is a rare cause of pulmonary thromboembolism. Our experience demonstrates a massive pulmonary thrombus resulting from such a deficiency. Transthoracic echocardiography should be considered as the first diagnostic method for patients with suspected pulmonary embolism.