OBJECTIVE To study the relationship between the expression of proto-oncogene bcl-2 and MTS1/p16 in transitional cell carcinoma of bladder and prognosis. METHODS Immunohistochemical SABC method was used to detect the expression of proto-oncogene bcl-2 and MTS1/p16 in 51 paraffin-embedded primary transitional cell carcinoma of bladder specimens and 5 normal bladder mucosa specimens. RESULTS The positive expression of bcl-2 was seen in 80.2% (42/51) tumors. There was statistically significant correlation between prognosis and the positive expression of bcl-2. The positive expression rate was higher in tumors with poorer prognosis than in those with better prognosis (P < 0.05). The expression of p16 protein was positive in 50.9% (26 of 51) in tumors and negative in all 5 normal bladder mucosae. The positive expression rate of p16 descended with increasing grade, stage and poorer prognosis. Clinicopathological characteristics and prognosis were related to the expression of p16 (P < 0.05). The positive expression of bcl-2 versus negative expression of p16 were seen in 20 of 51 of tumors, with distributing grade I 3/11, grade II 9/26, grade III 8/14, Tis - T(1) 6/28, T(2) 10/17, T(3) 4/6, A group 5/20, B group 4/16, and C group 11/15, respectively. Both bcl-2 and p16 were positively expressed in 22 of 51 of tumors. Their positive expressions were higher in tumors with lower grade, stage and better prognosis than in those with worse clinicopathological characteristics and poorer prognosis (P < 0.05). CONCLUSIONS Over-expression of bcl-2 appears to be common in bladder cancer; over-expression of proto-oncogene bcl-2 and inactivation of the MTS1/p16 gene are likely to be contributing factors for primary bladder cancer; and they can be the prognostic indicators for transitional cell carcinoma of urinary bladder.