P63 is essential for the differentiation of normal urothelium and is also expressed in transitional cell carcinoma (TCC) of the bladder. We investigated p63 immunoreactivity in upper urinary tract TCC (n=53) and in renal-cell carcinoma (RCC; n=188) using a tissue microarray technique. P63 expression was detected in 51/53 (96.2%) TCCs, showing decreased expression in high-stage (pT1 and pT2 100%; pT3 90.9%) and poorly differentiated (G1 and G2 100%; G3 92%) tumors. All RCCs were negative for p63. P63 proved to be a helpful tool, even in poorly differentiated and undifferentiated renal malignancies, to distinguish TCC from RCC.