Squamous Cell Carcinoma (SCC) is a prevalent form of skin and oral cancer, characterized by the uncontrolled growth of abnormal squamous cells in the epidermis. This chapter provides a comprehensive overview of the pathophysiology, diagnosis, and treatment of SCC, emphasizing the predisposition factors that contribute to its development. The pathophysiology involves mechanisms such as UV radiation exposure, genetic predisposition, chronic inflammation, and viral infections. UV radiation, particularly from sunlight, causes DNA damage and mutations in tumor suppressor genes, while genetic predisposition and inherited syndromes such as xeroderma pigmentosum and epidermolysis bullosa increase susceptibility to SCC. Chronic inflammation, immunosuppression, exposure to chemical carcinogens, and certain viral infections also contribute to SCC development. SCC represents a significant health concern, necessitating a comprehensive understanding of its predisposition factors, pathophysiology, accurate diagnosis, and appropriate treatment approaches. By elucidating the complex interplay between genetic and environmental factors, advancements in diagnosis and treatment can be made, leading to improved patient outcomes and a reduction in the burden of SCC on public health. Increased awareness, early detection, and access to effective treatments are key in mitigating the impact of SCC and improving overall prognosis for individuals affected by this condition. © 2024 Elsevier B.V., All rights reserved.