Background. Cryopeeling is a technique that uses cryotherapy not only on actinic keratoses lesions, but also all over the photodamaged skin. Objectives. To investigate the histological changes induced by two cryopeeling methods (liquid nitrogen (LN) and portable system (PS)). Methods. Sixteen patients (n = 16) with multiple actinic keratoses on the forearms were treated with cryopeeling technique using LN for one forearm and PS for the other, randomly. Skin biopsies were taken before and after the procedures. Results. There was no statistical difference between the epidermal and Grenz zone thicknesses or density of elastic fibers after treatments. The amount of melanin pigment was lower after PS treatment (P < 0.05). In a blind analysis of paired pre- and postprocedure slides, it was not possible to identify cases which underwent treatment, both in global analysis of quality of the skin and in specific analysis (considering only the aspect of stratum corneum). Discussion. The results indicate the inconsistency of histological improvement after treatments, and, likely, since the method causes superficial exfoliation, a reliable marker was not found in the analysis. Conclusions. Despite cosmetic benefits on photodamaged skin and efficient treatment of actinic keratoses lesions, cryopeeling was not able to induce measurable histological changes in solar elastosis, epidermal organization, or epidermal and Grenz zone thicknesses. One should keep in mind the possibility of hypopigmentation risk of the method.