Actinic keratoses (AKs) are common dysplastic lesions resulting from chronic excessive ultraviolet exposure. Neither the clinical grade of thickness nor the histological grade of dysplasia seems valid predictors of aggressive potential of AKs. Instead, the mutational status in AKs appears to predict well the clinical course. TP53 gene mutations result in a non-functional protein resistant to degradation, thus immunohistochemical staining for p53 can suggest mutation status. Increased p53 was associated with progression from AK to squamous cell carcinoma. To investigate how the intensity of p53 staining (p53 staining index) varies according to body site, histological subtype and grade dysplasia of AKs. Secondly, we sought to investigate the distribution in the epidermal layers of non-functional p53 (zonal staining patterns). p53 staining index was greater than 50% in 90.7% of AKs. p53 staining index was significantly higher in older age (p < 0.0093) and in facial AKs compared to other body areas (p = 0.03). A significant correlation between p53 staining index and grade of dysplasia was observed (p = 0.006) and between p53 staining index and zonal p53 staining pattern (p = 0.003). No significant differences in p53 staining index among the various histological AK types were observed. No correlation between clinical and histological grade. All AKs, independently from their clinical appearance, should be treated but special attention is required for AKs on severely photodamaged skin on the face and in older patients.