In patients with metastatic vulvar cancer, we found no common intracellular transduction pathway mutations; rather, mutations were found in TP53, c-KIT, BRAF, and KRAS. One patient with metastatic KRAS wild-type squamous cell carcinoma experienced stable disease for about 11 months after being treated with epithelial growth factor inhibition-based phase I trial regimens, while another patient had stable disease for 6 months after being treated with erlotinib and valproic acid. Here, KIT is linked to squamous cell carcinoma.