The diagnosis of renal cell carcinoma (RCC) remains problematic, especially in the context of metastasis or small needle biopsy specimens. The renal cell carcinoma marker (RCCM) and kidney-specific cadherin (KSC) are considered specific markers for RCC but are expressed preferentially in specific subtypes of RCC of lower grades. This study was aimed at evaluating the usefulness of PAX-2 in the diagnosis of renal tumors and comparing it with that of RCCM and KSC. Immunostaining for PAX-2, RCCM, and KSC was performed on consecutive tissue sections of 130 renal tumors. PAX-2 was successfully detected in routine tissue specimens. Although PAX-2 seems to be more sensitive than RCCM and KSC, there is significant staining overlap in relation to histologic subtypes, justifying the use of all 3 markers, which helps detect the vast majority of renal neoplasms. PAX-2 seems to have a significant role in renal neogenesis and may represent a novel therapeutic target.