Expression of c-kit has been demonstrated in 33% of adult nasopharyngeal carcinomas (NPCs) and in 88% of paediatric NPCs. Patients with tumours expressing c-kit tend to exhibit better survival, but a paracrine/autocrine function for the stem cell factor (SCF)/c-kit system in nasopharyngeal carcinomas has not been reported. This study evaluated the expression of c-kit and SCF by immunohistochemical staining of nasopharyngeal epithelium (NPE) and of primary and metastatic NPCs. In addition, c-kit and SCF expression were studied in HONE-1 NPC cells by immunoprecipitation and western blotting. Expression of c-kit and SCF was detected in 75% and 57% of NPE, respectively, and there was 48% co-expression. In primary NPCs, 86% expressed c-kit, 69% had SCF expression, and there was 67% co-expression. In metastatic NPCs, 76% expressed c-kit, 72% expressed SCF and there was 68% co-expression. Co-expression of c-kit and SCF with tyrosine autophosphorylation of p145(c - kit) was demonstrated in HONE-1 NPC cells. In addition, the expression level of c-kit and its autophosphorylation status was not obviously influenced by the transient co-expression of Epstein-Barr nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1). Co-expression of c-kit and SCF is therefore commonly found in nasopharyngeal epithelium and NPCs, and in HONE-1 NPC cells with autoactivation possibly independent of the co-expression of EBNA1 and LMP1. All of these findings suggest that autoactivation of SCF/c-kit signalling may be a potent regulator of the nasopharyngeal epithelial barrier and of immune function at the nasopharyngeal mucosa surface, and may contribute to the carcinogenesis and progression of NPC. Further molecular analysis is required to evaluate the possibility of treatment with tyrosine kinase inhibitors in NPC, analogous to the treatment of gastrointestinal stromal tumours with STI571.