The invention relates to methods and compositions for identifying mutations associated with cancer, such as melanoma. More particularly, the invention relates to methods and compositions for assessing particular mutations as markers for cancer, such as melanoma. Such methods and compositions allow medical providers to diagnose cancer, such as melanoma, based upon the presence of one or more particular mutations in a subject, as compared with an otherwise healthy control. The methods and compositions are also useful in guiding the type of therapy to be applied, and monitoring the effects of the therapy applied.