Squamous cell carcinoma on sun-damaged skin is a malignant neoplasm that evolves from its inception as squamous cell carcinoma in situ, which is commonly referred to as an actinic keratosis. In this study, we reviewed 1011 squamous cell carcinomas on sun-damaged skin and found that nearly 100% of these lesions contained histopathologic changes consistent with squamous cell carcinoma in situ at the periphery or within the confines of the squamous cell carcinoma. These malignant changes began in single layer areas of the lower epidermis and evolved into the epidermis and dermis.