A total of 66 bladder cancer patients were studied to verify possible relationships between HER-2/neu alterations and pathological characteristics, and to define a poor prognosis patient subgroup with respect to time to recurrence, time to progression and survival. Tumor and healthy tissue specimens were analyzed for HER-2/neu DNA amplification and protein overexpression by Southern and Western blot techniques and evaluated statistically. 13% of cases were amplified and 39% were overexpressed. HER-2/neu alterations were not significantly associated with pathological staging or tumor grading. Multifocal tumors had a higher percentage and overexpression with respect to monofocal tumors. Actuarial analyses did not show a significant statistical correlation between HER-2/neu amplification and overexpression and clinical outcome. Clinical evaluation of HER-2/neu status showed that this gene is not related to tumor relapse, progression or patient survival.