The present invention relates to method and composition for treating melanoma. The inventors have shown that a decrease in LYN expression, in melanoma cells and tumors is related to the acquisition of a resistance to targeted therapies. The have also shown the inhibition of metastatic propensity of melanoma cell by an allosteric activator of LYN. In particular, the present invention relates to a method for predicting whether a subject suffering from a melanoma is or is at risk of having resistant melanoma. The present invention also relates to methods for treating melanoma and resistant melanoma in a subject in need thereof comprising a step of administering said subject with a therapeutically effective amount of an activator of LYN.