Upper layers of the skin (epidermis) and is mainly due to chronic sun exposure. It is most common in white skin individuals mainly older than 50 years of age. Actinic keratosis, also known as a precancerous lesion, may progress to Squamous Cell Carcinoma. In healthy individuals, the rate of metastasis is low however not impossible. Patients that are immunosuppressed or on immunosuppressive medications may have an increased incidence of Squamous Cell Carcinoma.

Common areas include face, including tips of ears, scalp, upper extremities, trunk and shins (particularly in females). They clinically present as thick scaling lesions. They may be eroded or ulcerated and may bleed. A subset of Squamous Cell Carcinoma, known as Keratoacanthoma, may develop very quickly in a matter of 2 to 3 weeks. Squamous Cell Carcinomas must be treated early and appropriately in order to prevent the possible risk of metastasis.