Acantholytic squamous cell carcinoma (ASCC) of the mucosal membranes has been documented sporadically. The highly aggressive behavior of a mucosal ASCC arising in the oral cavity has been recently reported. To the best of our knowledge, only 1 autopsy case of maxillary ASCC previously has been reported in the literature. We pre-sent what we believe is only the second case of maxillary ASCC. Our goal is to emphasize the aggressive behavior of this tumor in order to add weight to the argument that the prognosis is poor.