Squamous cell carcinoma (SCC) is a rare disease in children showing low incidence and prevalence and accounting for <2% of all pediatric malignancies. A literature review reveals striking biologic differences between the pediatric and adult forms of SCC. The etiologic factors that are traditionally linked to the development of SCC in adults like tobacco, alcohol, viruses, and nutritional deficiencies do not always apply to the pediatric population in general. In children, etiologic factors include several hereditary conditions, unique molecular genetic alterations, environmental conditions, immunosuppressive states, certain dietary practices, poor oral health, and viral infections in specific demographic populations. Clinical findings depend on the primary tumor’s anatomical site and its etiology. In the last decades, there has been a progressive rise in the incidence of pediatric SCC due to the increased prevalence of Human Papilloma virus (HPV) infection, which has become a critical factor determining the clinical course and prognosis. In this multidisciplinary review, we discuss the epidemiology, etiology, and pathogenesis of SCC in the pediatric population and highlight differences in treatment and prognosis in contrast to adult tumors. Because of its rising incidence in children, increasing awareness is the key to early diagnosis and optimal healthcare outcomes.