For bladder cancer we currently lack accurate methods of predicting outcome, although clinical stage and histological grade are broad determinants of prognosis. Preliminary data have indicated that assessment of epidermal growth factor receptor status is a method of further subclassifying bladder cancer. We assessed prospectively the clinical significance of determining epidermal growth factor receptor status in 212 patients with newly diagnosed bladder cancer who were followed for 1 to 96 months (mean 26.5). In multivariate analyses epidermal growth factor receptor was confirmed to be an independent predictor of survival (p = 0.004) and stage progression (p = 0.0004). Most importantly, epidermal growth factor receptor status was found to be 80% sensitive and 93% specific in predicting stage progression in T1, grade 3 bladder cancer. We conclude that epidermal growth factor receptor status is a useful molecular marker in patients with bladder cancer, especially those without infiltration of the detrusor muscle at presentation.