Increasing experimental evidence indicates that stem-cell factor (SCF) and its cognate receptor c-Kit may participate in the growth control of various solid human malignancies. In the present study, we have extended this analysis to non-small-cell lung carcinomas (NSCLC). The results of an immunohistochemical analysis demonstrated that c-Kit/SCF are expressed by 30%/58% of adenocarcinomas, 15%/37% of squamous-cell carcinomas and by 40%/30% of undifferentiated carcinomas respectively. In 15% of primary and 18% of metastatic tumors, co-expression of the receptor and its ligand was documented. Western-blot assays of tumor extracts demonstrated that both molecules exhibit features of the normal receptor and ligand. Since biologically active SCF is physiologically present in the bloodstream, our data indicate that SCF is available to c-kit-expressing NSCLC cells via autocrine, paracrine or endocrine mechanisms. Thus activation of c-Kit in these tumors may contribute critically to their progression.