Oral adenosquamous carcinoma (ASC) is a rare and aggressive type of squamous cell carcinoma (SCC). It is characterized by a squamous component originating at the mucosa and a deep glandular component. ASC may be misdiagnosed as SCC by superficial incisional biopsy including only the squamous component. ASC has a worse prognosis than general variants of SCC, so accurate diagnosis is essential for patient survival. We present a case report of a large ASC arising in the buccal mucosa, first mistaken as general SCC.