Abstract Background Vascular endothelial growth factor-targeted therapy has been standard care for metastatic renal cell carcinoma for years. However, little clinical experience on these agents in the treatment of sarcomatoid tumors has been documented. The aim of the present study was to detect the expression of c-KIT in the primary tumor of metastatic renal cell carcinoma with sarcomatoid feature, and to reveal its potential value of predicting the efficacy of sorafenib treatment and survival of the patients. Patients and Methods Seventeen patients were enrolled and treated with sorafenib as a second-line treatment after cytokine therapy. The expressions of c-KIT was tested immunohistochemically in the 17 specimens of primary renal tumors. The correlation between c-KIT status and treatment effect was compared. Univariate and multivariate analysis were employed to determine the survival difference between c-KIT-positive and c-KIT-negative patients. Results Twelve of 17 specimens (70.6%) were detected to be overexpressing c-KIT. c-KIT positive patients had higher disease control rate (75%) compared with c-KIT-negative patients (25%), P = .036. Median overall survival time was 92 weeks for c-KIT positive patients and 44 weeks for c-KIT negative patients, log rank χ2 = 9.566, P = .002. Multivariate Cox regression model analysis only revealed number of metastatic organs and c-KIT as independent prognostic factors. Conclusion Our findings suggest that c-KIT can be a potential predictive factor for metastatic renal cell carcinoma with sarcomatoid feature in treatment using sorafenib, and patients with positive c-KIT expression might have better responses and obtain longer overall survival time.