Objective:To study the expression and clinical features of P53,Bcl-2,C-erbB-2 and (epidermal growth factor receptor,EGFR) in multiple primary bladder cancers and single bladder cancers,and provide evidence for diagnosis and targeted treatment of multiple primary bladder cancer. Methods:Immunohistochemical SP methods were used to detect the expression of P53,Bcl-2,C-erbB-2 and EGFR in 15 patients with multiple primary bladder cancers,15 patients with single bladder cancers(The clinical stage and pathological grade of patients with single bladder cancers were similar to those with multiple primary bladder cancers.) and 15 patients with normal bladder,the differences of the expression of P53,Bcl-2,C-erbB-2 and EGFR in each group were analyzed. Results:The positive expressions of P53,Bcl-2,C-erbB-2 and EGFR in patients with multiple primary bladder cancers and single bladder cancers were significantly higher than those in patients with normal bladders(P < 0.05). The positive expressions of P53 and Bcl-2 in multiple primary bladder cancer tissues were higher than those in single bladder cancer tissues(P < 0.05),while the positive expressions of C-erbB-2 and EGFR in multiple primary bladder cancer tissues were significantly lower than those in single bladder cancer tissues (P < 0.001). Conclusion:The positive expressions of P53,Bcl-2,C-erbB-2 and EGFR were different between multiple primary bladder cancers and single bladder cancers (P < 0.05). The combined detection of P53,bcl-2,C-erbB-2 and EGFR is valuable for the clinical diagnosis and identification of multiple primary bladder cancers. This study provides the possibility of the targeting therapy of multiple primary bladder cancers.