OBJECTIVE: To determine serum levels of standard CD44 (sCD44s) and its variant isoform, sCD44v6, in patients with bladder cancer and to assess their relationship with the invasiveness of bladder cancer. MATERIALS AND METHODS: Serum concentrations of sCD44s and sCD44v6 in 77 bladder cancer patients were determined by an enzyme-linked immunosorbent assay. Invasiveness of the tumor was classified using the TNM staging system. RESULTS: Concentrations of sCD44s progressively decreased as 414.0±205.1, 277.7±138.9, 186.8±18.8 and 115.7±28.7 μg/L, respectively from stages Ta-1, T2, T3, to Mi. Levels of sCD44v6 also showed a similar decreasing tendency of 205±128.7, 132.7±18.3, 84.2±5.6, and 78.7±5.8 μg/L, respectively. The statistical analysis was marginally nonsignificant (p=0.06). CONCLUSIONS: Trends of decreasing sCD44s and sCD44v6 feature a progressive loss of immunoreactivity in association with tumor dedifferentiation, resulting in an advancing pathologic stage.