The mutations of c-kit gene, which encodes a transmembrane receptor tyrosine kinase (CD117-KIT) or activation of CD117, lead to the activation of signal transduction cascades regulating cell proliferation, apoptosis, chemotaxis, and adhesion. The aim of this study was to investigate the expression of CD117 in normal, inflammatory, neoplastic, and reactive lesions of the thyroid. Using polyclonal anti-CD117 antibody, we performed immunohistochemical staining on tissue blocks from 230 cases obtained from the archives of the Department of Pathology, Ondokuz Mayis University (Samsun, Turkey), collected between 1990 and 2006. Each slide was evaluated for extent and intensity of staining. Staining extent was expressed as the percentage of stained cells. Staining of <10% of the cells was accepted as negative. Staining intensity was evaluated only in positive cases. By addition of the extent and intensity scores, the combined score was calculated. In our study, the combined CD117 staining scores of neoplastic and inflammatory groups were found to be higher than the reactive and normal groups. Within the neoplastic group, papillary carcinomas differed from follicular adenomas significantly, although papillary carcinomas showed no statistically significant difference compared to follicular carcinomas. Immunohistochemical CD117 positivity was detected in a wide range of neoplastic and inflammatory thyroid diseases. The neoplastic group and, within them, the papillary carcinomas showed a higher ratio of CD117 positivity. Although our results need to be confirmed by other molecular and genetic studies, the high rate of positivity in papillary carcinomas was one of the striking findings, which may result in novel diagnostic and therapeutic approaches.