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Background: Actinic keratoses (AKs) are considered to be a ‘field of cancerization’ consisting of a histologically abnormal epithelium adjacent to tumour tissue. Treatment of the ‘field of canceri-zation’ is important for the prevention of neoplasm progression. UV radiation, especially UVB, produce genotoxic photoproducts such as cyclobutane pyrimidine dimers (CPDs) and 6-4 photo-products (6-4PPs) in DNA, being major players in skin cancerization. The potential use of DNA photolyases in skin cancer prevention is increasingly being demonstrated. Topical application of a liposome formulation containing CPD photolyase onto human skin provides protection against UV-B-induced damages. Objectives: To assess the effects of topical application of a medical device (Eryf-AK) containing a DNA-repair enzyme, photolyase, encapsulated in liposomes and UV filters, on cancerization field in actinic keratosis (AK). Methods: 13 AK patients were included. Clinical, dermoscopic, and reflectance confocal microscopy (RCM) assessments, as well as skin biopsies, before and after a 4-week treatment were performed. Patients used Eryf-AK twice daily or only a sunscreen (3:1) with a similar sun protection factor (SPF) for one month. Results: Erythema and scaling improved with Eryf-AK. RCM showed a reduction in scaling, detached corneocytes and polygonal nucleated cells in the stratum corneum (p=0.004, p=0.018, and p=0.021), an improvement of the atypical honeycomb pattern, and a decreased number of round nucleated cells at the spinous granulous layer (p