The present study attempted to clarify the significance of aberrant expression of β-catenin protein and mutation of exon 3 of the β-catenin gene in renal and urothelial carcinogenesis. β-Catenin expression was examined immunohistochemically and mutation of the β-catenin gene was analyzed by polymerase chain reaction-single strand conformation polymorphism (SSCP) and direct sequencing. β-Catenin immunoreactivity was observed at the cell membrane in all 30 renal cell carcinomas (RCC) examined, and no RCC showed a mobility-shifted SSCP band. Of 46 transitional cell carcinomas (TCC) examined, there was reduced expression of β-catenin, as compared with its expression in non-cancerous transitional epithelium, in 22 cases (48%) and β-catenin accumulation in the nucleus in five cases (11%). Of four renal pelvis TCC examined, point mutation of exon 3 of the β-catenin gene at codon 45 resulting in amino acid substitution (Ser to Phe) was detected in one (25%). The incidence of reduced expression of β-catenin correlated significantly with the growth pattern (superficial type vs invasive type) of TCC (P< 0.05). These data indicate that: (1) aberrant β-catenin expression may be at least partly involved in urothelial carcinogenesis, but less significantly so in renal carcinogenesis, and (2) it may be associated with the progression of TCC showing invasive growth.