Adenoid squamous cell carcinoma (ASCC) is a rare variant of squamous cell carcinoma. This tumor most commonly occurs in the skin of the head and neck and rarely in the vermillion of the lip, vulva, and oral cavity. This report of two patients includes the first (to our knowledge) case of ASCC in the nasopharynx. It also describes the immunocytochemical and ultrastructural features of this tumor. Our findings and a review of the literature indicate that ASCC of the upper aerodigestive tract is associated with an aggressive behavior and poor prognosis, in contrast with ASCC of the skin.