This is the first documented case of spontaneous intermittent preexcitation associated with mesothelioma of the atrioventricular (AV) node. A 66-year-old male with recurrent atrial arrhythmias, palpitations, heart failure, and marked intra-atrial conduction defect that required a pacemaker died during sleep. Electrophysiologic study revealed left free-wall bypass tract with marked intra-atrial conduction defect and prolonged conduction across the bypass tract. With atrial pacing, high degrees of block were noted in the bypass tract. Serial section of the conduction system and both AV rims revealed two left posterior and lateral bypass pathways with patchy areas of fibrosis. A large mesothelioma (benign AV nodal tumor) almost completely replaced the AV node. In addition, there was marked fatty infiltration of the atria. In summary: (1) the intermittent preexcitation with prolonged conduction across the bypass tract and block with atrial pacing were probably related to the incomplete patchy degenerative changes in the bypass tract, and/or almost complete replacement of the AV node by the tumor; (2) the intra-atrial conduction defect was probably related to the replacement of the AV node by mesothelioma and/or the fatty infiltration of the atria; and (3) the paroxysmal atrial arrhythmias probably reflect the marked atrial pathology.