AbstractThe most common diagnosis rendered with head and neck fine needle aspiration (FNA) biopsy is metastatic squamous cell carcinoma (SCC). While most cases of metastatic SCC pose little diagnostic difficulty, the diagnosis of metastatic histologic variants of SCC, often coupled with less common etiologies, can be more problematic. This manuscript reviews the clinicopathologic features of the histologic variants of upper aerodigestive tract SCC (verrucous, papillary, spindle cell, undifferentiated, acantholytic, and basaloid) and uncommon etiologies of head and neck SCC (human papillomavirus, Epstein‐Barr Virus, and NUT midline carcinomas). Particular attention is paid to the cytologic features of these lesions. Differential diagnoses and the use of ancillary testing are discussed. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.