Molecular markers to help stratify risk in patients with high-grade bladder cancer would be helpful to determine which patients require prompt radical cystectomy. p63, p53 and ΔNp63 expression were analysed in 134 high-grade tumours, with progression to muscle-invasive disease or cystectomy as the end points. 21.1% of patients with ΔNp63 loss experienced progression, compared with none of those expressing ΔNp63. ΔNp63 could, therefore, be used to identify those patients at very low risk of progression who can receive transurethral resection and BCG and do not require immediate cystectomy.