Renal tumor cell invasion is responsible for both local destruction and distant metastasis. The overexpression of c-KIT in chromophobe renal cell carcinoma (ChRCC) has been described by comparative immunohistochemical analyses and has been proposed as a possible specific hallmark of this neoplasm. The aim of our study was to establish its immunostaining score in tissue microarrays of ChRCC and to compare it with other renal neoplasms. We hypothesize that c-KIT is overexpressed in renal tumors. Methods: Immunostaining score analysis of c-KIT was performed in tissue microarrays of 68 renal neoplasms, including 12 cases of chromophobe renal cell carcinoma (ChRCC), 34 cases of clear cell RCC (CRCC), 13 cases of CRCC with granular cell differentiation (GRCC), one case of papillary RCC, one case of collecting duct RCC, three cases of nephroblastoma, and four cases of transitional cell carcinoma. Results and Conclusions: ChRCC, nephroblastoma and transitional cell carcinoma showed significant immunostaining scores for c-KIT when compared to normal renal fibrovascular tissue. The immunostaining score in ChRCC (323±22) was higher than other histological subtypes of RCC (7±4 for CRCC; 4±4 for GRCC; 4 for papillary RCC; 100 for collecting duct RCC). The meaning of increased immunostaining score for c-KIT in ChRCC is still unknown, but its immunostaining score appears to be useful in distinguishing ChRCC from CRCC, GRCC, papillary RCC and collecting duct RCC. No correlation was noted between the c-KIT immunostaining scores and Fuhrman nuclear grade. Finally, we demonstrated for the first time in a tissue microarray system that c-KIT is overexpressed in ChRCC, nephroblastoma and transitional cell carcinoma, and that targeted therapy with STI-571 may be beneficial to these tumors.