OBJECTIVE To examine the expression of CD44 isoform v10 (CD44v10) in patients with renal cell carcinoma (RCC), analyse its role in RCC and its relationship with conventional clinical-histopathological experience. Materials and methods Sixty-four RCC specimens and five metastatic specimens were analysed immunohistochemically using a CD44v10 specific antibody. The expression of CD44v10 was compared with the histological grade and clinical or pathological stage of the tumours. RESULTS Of the 64 primary tumour specimens, 22 (34%) expressed CD44v10 protein; all of these positive specimens were clear-cell and mixed-cell RCC. Staining was also positive in four of five metastatic specimens and negative in all four cases of granular cell carcinoma. CD44v10 expression was significantly correlated with the histological grade (P<0.0001), clinical stage (P = 0.0050) and pathological stage (P = 0.0143) of the tumours. The prognosis for patients with clear-cell RCC who were CD44v10-positive was worse than for patients who were CD44v10-negative (P<0.0001). In subgroups with different tumour stage (< or =pT2 or > or =pT3), the prognosis for patients with positive CD44v10 expression was also worse than for those with no expression (P<0.05). CONCLUSIONS The expression of CD44v10 correlated significantly with histological grade, clinical and pathological stage, and with survival in patients with clear-cell RCC. CD44v10 protein may play a role in the progression of clear-cell and mixed-cell RCC, and thus the analysis of CD44v10 expression may provide useful prognostic information.