Background: There are three types of non-melanoma skin cancer (NMSC): basal (BCC), keratoacanathoma (KA), and cutaneous squamous cell carcinoma (cSCC). These three malignancies account for 99 percent of all tumors in this category. Because it slows DNA synthesis in quickly proliferating cells, methotrexate (MTX) is an effective treatment for tumors that are fast developing. To prevent the production of the purine nucleotide thymidine, it inhibits the development of tetrahydrofolate by binding to the dihydrofolate reductase. Objective: To assess the efficacy and safety of MTX in the treatment of NMSCs. Conclusion: When used as a less intrusive and less expensive treatment for NMSCs, MTX has the potential to be a very effective and safe alternative treatment, especially in patients who are elderly or have other medical conditions.