OBJECTIVE: To investigate efficacy of masitinib mesylate for the treatment of advanced malignant melanoma in dogs. MATERIALS AND METHODS: Prospective clinical trial on 17 dogs with stage III and IV malignant melanoma (two digital, one anal and 14 oral mucosal). Only dogs with advanced gross disease for which the owner declined conventional treatment or dogs with progressive tumour despite conventional treatment were included. RESULTS: There was a partial response in two dogs, stable disease in seven and tumour progression in eight dogs. Median survival time for all 17 dogs was 119 days (range 21-255). Masitinib was generally well-tolerated but grade 2 anaemia, grade 1 neutropenia, grade 1 diarrhoea and grade 2 anorexia were observed in one dog each. CLINICAL SIGNIFICANCE: There was only mild effectiveness in end-stage disease, indicating that masitinib mesylate is not an appropriate sole-agent option for treatment of advanced malignant melanoma in dogs.