Recently, the potential risk of malignant cancer development in psoriatic patients has been highlighted. However, the relationship between the therapeutic schemes in psoriasis and possible neoplastic transformation has not been so far clearly explained. Phototherapy is considered a very effective therapeutic method in psoriasis, however, the pathogenesis of some malignancies may be associated with the exposure to UV radiation. p16 protein belongs to the defense mechanisms that protect cells from damage and mutagenic factors, such as UV radiation. In recent years, the altered expression of the p16 protein in the diseases not related to malignant transformation, including psoriasis, has been observed. These new observations suggest participation of the p16 protein in the mechanisms of psoriatic plaque formation.