Squamous cell skin cancer is the second most common malignant skin lesion and has varying presentations from differences in color, ulceration, etc. Squamous cell skin cancer also is noted to have a precancerous lesion known as actinic keratosis (solar keratosis, senile keratosis) which is described as thick, scaly, crusty plaque. P53 genetic mutations are the most common mutation in this form of cancer. This chapter is based off of the most up-to-date NCCN Guidelines (Version 1.2024).