Saenz–Sarda X, et al. – The variations between the classical and differentiated pathways in the pathogenesis of actinic keratosis (AK) were comprehensively evaluated, emphasizing on Ki67, p53, p16 and molecules that disclosed epithelial mesenchymal transition. It was deduced that the epithelial mesenchymal transition aided in the transformation from atypia at the basal layers of the epidermis (AK I) into invasive squamous cell carcinoma (iSCC) (differentiated pathway). In contrast, a higher proliferative capacity enabled the intraepidermal extension in the classical pathway. Podoplanin, also involved in tumour invasion, did not play a differential role in either pathway. The lack of variations in p53 and p16 expressions were at variance with other epithelia, where the classical pathway correlated with human papillomavirus infection. It was elucidated by both AK pathways sharing identical mechanisms of actinic oncogenesis.