['To date, studies with ingenol mebutate gel have used clinical clearance, not histological clearance, as a primary efficacy endpoint.', 'This phase I, multicentre, single-arm, open-label study sought to confirm histologically the clinical clearance of actinic keratoses (AKs) to support a treatment effect deep in the epidermis.', 'Patients (n = 108) aged ≥ 18 years with histologically confirmed AK within a 25-cm', 'The observed agreement rate between clinical and histological assessments of clearance of a single AK was 81·9% and the positive predictive value of a clinical assessment of clearance was 87%. Agreement between the two pathologists was 88%. The common composite 8-week complete clearance rate was 41% (95% confidence interval 32-50). Observed agreement rates between RCM and pathologist I and II assessments of clearance were 72·9% and 81·4%, respectively. Overall, 30 patients (27·8%) experienced 38 adverse events (AEs). Application-site pain (four patients, 3·7%) was the most common treatment-related AE inside the treatment area.'] Does histological examination confirm clinical clearance of actinic keratoses following treatment with ingenol mebutate 0·05 % gel?