Melanoma is the deadliest form of skin cancer and is increasing in incidence. Recent treatment advances have been made, but there remains a need for continued development of effective therapy options, as treatment rarely leads to cure. Many melanomas contain somatic mutations involved in tumor pathogenesis. Accurate identification of these mutations is necessary to stratify patients for the purpose of treatment and potential for clinical trials, given the absence or presence of a specific mutation. There are a number of techniques available that will identify genetic mutations and genomic aberrations present within melanoma tumor samples which are reviewed here. The type of mutation and sample number will drive selection of a given mutation detection strategy. The strengths and weaknesses, along with limitations, of the various methods will also be discussed. The discovery of somatic mutations integral in melanoma will increase our understanding of tumor pathogenesis and should facilitate identification of mutations relevant to clinical treatment decisions, advancing progress toward personalized medicine.