Basaloid squamous cell carcinoma is a recently recognized variant of squamous cell carcinoma. The lesion is histologically distinctive and manifests a predilection for the supraglottis, pyriform sinus, and tongue base. The immunohistochemical profile is discussed. The differential diagnoses include adenoid cystic carcinoma, small cell neuroendocrine carcinoma, basal cell adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma, spindle cell squamous carcinoma, mucoepidermoid carcinoma, and adenoid squamous cell carcinoma. Basaloid squamous cell carcinoma is a biologically high-grade tumor with a propensity for nodal as well as systemic metastases. It is a morphologic and phenotypic entity with a separate prognostic significance.