It has been reported previously that BCL2 expression predicted a poor response to neo adjuvant chemotherapy but had no prognostic significance in patients receiving radiotherapy alone. We therefore investigated its role in patients receiving synchronous chemoradiotherapy as treatment for advanced bladder cancer. We examined expression of BCL2 and P53 by immunohistochemical analysis using archival tissue samples taken from patients included in the phase I/II trial of synchronous chemoradiotherapy for advanced transitional cell carcinoma (TCC) of the bladder. Data were collected on 24 patients who presented with invasive bladder cancer to the Queen Elizabeth Hospital between March 1998 and January 2001. Eleven patients had died at the time of analysis, with median follow-up of 34 months for the 13 surviving patients. Median survival for patients with strongly BCL2 positive tumours was 12.8 months while, for BCL2 weak or negative patients, the median is yet to be reached (p=0.03). The hazard ratio was 3.37 in favour of BCL2 negative tumours having longer survival. This study shows that over-expression of BCL2 in patients receiving synchronous chemoradiotherapy is an independent indicator of poor survival in muscle invasive TCC of the bladder.