BACKGROUND: Individuals with medical history of non-melanoma skin cancers (NMSCs) usually develop multiple and/or recurrent malignant lesions around the site of the primary neoplasm. The latter represents the clinical expression of the 'field cancerization' theory; supporting the presence of multiple malignant clones of dysplastic keratinocytes over the entire epithelium that potentially can progress into clinical lesions. Taking into consideration that the burden of NMSCs on public health and health-care cost is high, adequate control of recurrences and management of field change is challenging.OBJECTIVES: To compare the safety and efficacy of daylight photodynamic therapy (DL-PDT) vs. conventional photodynamic therapy (C-PDT) in the prevention of occurrence of new NMSCs in patients with clinical and histological signs of actinic field damage.METHODS: Twenty-six patients, with personal history of NMSCs on the face or scalp and actinic keratosis (AK) on the same fields, were randomized for DL-PDT on one side and C-PDT on the other. For a 12-month period, individuals were clinically evaluated for development of new NMSCs.RESULTS: The total number of new AKs and the mean time of their development did not significantly differ between the treated sides. Local adverse events were more intense with C-PDT, and patients' preference was more for DL-PDT compared to C-PDT.CONCLUSIONS: The current findings suggest equal preventive potential of DL-PDT vs. C-PDT against the formation of new NMSCs in patients exhibiting actinic field damage.