Large cell neuroendocrine carcinoma and basaloid squamous cell carcinoma are each rare but aggressive diseases of the head and neck. A case of large cell neuroendocrine carcinoma occurring simultaneously with a basaloid squamous cell carcinoma originating from the oral cavity is described in this report. The diagnosis of these pathologies can be challenging but is important, as staging and treatment recommendations differ from those for oral cavity squamous cell carcinoma.