Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributedto chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT,encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, hasnot been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical(IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained fromthe Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for stainingintensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detectedin 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%)and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensityrespectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without(95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The highrate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for sitespecific immunotherapy to improve the outcome of this tumor.