Given the increase in luciferase activity indicative of Notch activity in cells transfected with CYLD siRNA, we explored the consequences of CYLD inactivation in skin tumours from patients with germline mutations in CYLD. This model was used to determine if features associated with increased Notch signalling such as the expression of Notch target genes were demonstrated in a human CYLD defective model, as suggested by the luciferase assay. Here, CYLD is linked to skin neoplasm.