Melanoma is an aggressive malignancy with a poor prognosis. Current studies show that imatinib treatment is a promising approach in treating advanced melanoma patients harboring c-Kit mutations or amplifications. We retrospectively analyzed the clinical medical records of 78 patients with metastatic melanoma harboring c-Kit mutations or amplifications. These patients were treated with imatinib at a dose of 400 mg/day continuously unless intolerable toxicities or disease progression occurred. Endpoints for exploration included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease of control rate (DCR). The median OS and PFS of all patients were 13.1 and 4.2 months, respectively. ORR and DCR were 21.8% and 60.3%, respectively. The survival time of patients who achieved partial response or stable disease was significantly superior to those with disease progression. Cox regression analysis showed that patients with M1c stage, subtype of cutaneous melanoma, or elevated LDH level (>upper limit of normal) had higher hazard ratios for overall survival. Our study, combined with those studies targeting patients with a c-Kit alteration, validates the role of imatinib as an important and promising therapeutic agent in the treatment of patients with advanced melanoma.