We examined metallothionein (MT) expression in bladder cancer and its relationship to clinicopathologic factors, survival data, and outcome of chemotherapy. In 97 patients who underwent radical cystectomy for bladder cancer, 34 of whom received cisplatin-based chemotherapy, MT expression was evaluated immunohistochemically. Results were correlated with histopathologic data, survival rates, and outcome of chemotherapy. MT overexpression was present in 33 patients (34.0%): strong in 7 (7.2%) and focal in 26 (26.8%). Overexpression was an independent prognostic factor and was significantly associated with poor survival. Patients undergoing chemotherapy showed worse survival if their tumours were MT-positive than if they were MT-negative. MT overexpression predicts unfavorable survival in bladder cancer patients. In those treated with cisplatin chemotherapy, survival is significantly poorer if tumours express MT. Our results show that MT overexpression may mediate resistance to alkylating agents. Therefore, further studies are warranted to define those patients who need a more aggressive therapy.