OBJECTIVES: Non-melanoma skin cancer rates are increasing worldwide and annually 2-3 million cases of non-melanoma skin cancer are being reported. Mohs micrographic surgery and surgical excision are two treatment methods for this type of cancer. Regarding the fact that the results concerning the cost effectiveness of these methods are inconclusive.The current paper aims at determining and comparing the cost-effectiveness of surgical excision and Mohs micrographic surgery. Based on the results of this paper amore cost-effective method for treatment could be determined. METHODS: The current study has a retrospective cohort design. A number of 630 patients suffering from non-melanoma skin cancer who at some point of time during the years 2007-10 referred to Al-Zahra or Seyyed Al-shohada hospitals in Isfahan were followed up for four years and then the incremental cost effectiveness ratio (ICER) of the two methods were calculated. RESULTS: The Average cost of the surgical excision and Mohs surgery methods in Iran was obtained as 185501670 ($618.7) and 12236890 ($408.1) Iranian Rials, respectively. Recurrence percentage was also reported as 7.9% and 8.7% for surgical excision and Mohs micrographic surgery, respectively. The incremental cost effectiveness ratio of surgical excision in comparison with Mohssurgery was calculated as 7891600 ($263.2) Iranian Rails per recurrence avoided. CONCLUSIONS: Since no significant difference was seen between the two methods and regarding the fact that Mohs surgery is less expensive than surgical excision, it seems like Mohs is more affordable, however further studies in different populations of the country are needed.