OBJECTIVES Actinic Keratosis  (AK) is the most common neoplastic lesion of the skin, its prevalence in Italy is 1.4% in the adult population, over the age of 45 years. The objective of this study is to evaluate through the development of a decision-tree model, the impact in terms of cost-effectiveness of treatment of patients with actinic keratosis (on the face), of ingenolo mebutato gel vs. imiquimod cream. METHODS The effectiveness was expressed in terms of utility; the ratio of cost effectiveness was expressed in terms of cost per Quality Adjusted Life Years (QALYs). The time horizon of the simulation was 12 months. For ingenolo mebutato was considered the price to the public starting from the ex-factory price currently lower in Europe (Spain price), while for imiquimod has been adopted the reference price, because of the drug generication. It was also considered the adherence rate of patients to the two treatment alternatives, due to the different duration of treatment (2-3 days Vs. 4-8 weeks) and adverse events, which in the case of imiquimod may persist for all the therapy lenght. RESULTS Based on these assumptions, ingenolo mebutato therapy is found to be less expensive and more effective, and so dominant, compared to imiquimod. The cost-effectiveness analysis has been tested with univariate sensitivity analysis, which confirmed the validity of the base case. CONCLUSIONS Based on these statement, it seems clear that ingenolo mebutato, due to its way of administration combined with its expected cost, represents a rational investment for the treatment of AK in the landscape of our national health system.