The aim of this study was to investigate whether levels of Fas and Fas-ligand (Fas-L) expression in oral and oropharyngeal squamous cell carcinomas (SCCs) are associated with tumor stage and grade, and to assess whether parameters related to argyrophilic nucleolar organizer regions (AgNORs) correlate with apoptosis in SCC cells and adjacent normal epithelium. Fifty-two specimens taken from the tumoral and neighboring normal tissues of 26 patients with oral and oropharyngeal SCC were analyzed for Fas/Fas-L expression, and 24 specimens from 12 patients for AgNOR parameters. Seventeen (65%) of the tumors were Fas and/or Fas-L-positive (by immunohistochemistry). A significant positive correlation was found between Fas/Fas-L expression and clinical tumor stage (P < 0.01). Mean AgNOR number per nucleus, AgNOR size and the percentage area of each nucleus occupied by AgNORs (percent of nuclear area) were significantly increased in the SCC cells (4.49 ± 1.28, 4.48 ± 1.42, 5.56 ± 1.22, respectively) when compared with the control neighboring squamous epithelial cells (2.58 ± 0.61, 1.64 ± 0.59 and 4.35 ± 0.62%, respectively) (P < 0.01). A significant positive correlation was found between the AgNOR parameters and Fas/Fas-L expression as apoptotic markers in the tumoral cells of SCC (P < 0.05). There was also a significant positive correlation between the AgNOR parameters and the grading of tumors (P < 0.05). In conclusion, AgNOR count was a strong proliferation marker in patients with SCC, and Fas and Fas-L staining was useful in tumor grading. © 2005 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.