Alteration of p53 gene and the molecular biological difference between superficial and invasive bladder cancer were investigated by polymerase chain reaction-single strand conformation polymorphism analysis and direct sequencing technique. p53 gene mutations were examined in exon region 5 to 8 in 21 bladder cancers. Only one of 14 superficial bladder cancers was found to have p53 gene mutation. Four of 7 invasive bladder cancers with T2, T3 and T4 were found to have p53 gene mutation. p53 gene mutation was found none of the 4 cancers with grade 1, only one of cancers with grade 2, four of 12 cancers with grade 3. These results suggest that p53 gene play an important role in the development of human bladder cancer.