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Non-melanoma skin cancers (NMSCs), including basal and squamous cell carcinomas, represent the most common malignancies among Caucasians. Over two million cases of NMSC occur each year in the US, with a progressive increase in incidence. There are well-known environmental risk factors, such as iatrogenic or ionizing radiation exposure, but the effect of chronic ultraviolet radiation, especially ultraviolet B radiation, is one of the main predisposing factors. Currently, based on our knowledge of the pathophysiology of most NMSCs, we have a better understanding of the associated genetic risk factors. The aim of this study was to evaluate the factors that contribute to the onset of NMSC through a comprehensive literature research.