Mesothelial/monocytic incidental cardiac excrescence (MICE) is a benign lesion composed of a haphazard mixture of mesothelial cells, histiocytes, and fibrin, often found incidentally during cardiac valve replacement. Its pathogenesis is controversial with some authors favoring an artifactually produced amalgam while others espoused a reactive phenomenon. Clinically, this entity is important because of potential misdiagnoses as malignancies. We report a case in a 65-year-old man with severe acute aortic regurgitation. A 2.0-cm mobile aortic valve vegetation was documented by transesophageal echocardiography prior to any cardiac instrumentation. At surgery, the lesion was immediately visualized together with free-floating vegetation in the left ventricular outflow tract. Routine and immunohistochemical examination showed a nodule composed of predominantly histiocytes and mesothelial cells, together with fibrin and scattered neutrophils. To our knowledge, this is the first reported case of a mesothelial/monocytic cardiac excrescence causing acute cardiopulmonary failure. The literature on MICE is reviewed with discussion of its etiology.