The pathogenesis of cutaneous squamous cell carcinoma is associated with multiple local genetic alterations that may bring about dysregulation of the cell cycle, of apoptosis, of DNA repair, of cellular differentiation, of telomerase activity with evasion of cellular senescence, and of expression of the enzyme cyclo-oxygenase 2 (COX-2). The gene discussed is PTGS2; the disease is cutaneous squamous cell carcinoma.