In this study, it is found that c-KIT c.1926delA p.K642S*FS mutation in primary and metastatic tumors of the GIST patients and c.1936T>G p.Y646D point mutation in melanoma cases were rare targets resistant to imatinib mesylate, which was identified using Sanger sequencing and cell culture experiments. The gene discussed is KIT; the disease is metastatic neoplasm.