The TNM staging categories and groupings of the updated 2009 American Joint Committee on Cancer (AJCC) Melanoma Staging System are outlined in Tables 6.1 and 6.2 [1]. “T ” parameters are defined by primary tumor thickness, ulceration, and mitotic status; “N” parameters by the number of lymph nodes with metastatic disease and extent of metastatic burden; and “M” parameters by the site(s) of the metastases and serum lactate dehydrogenase (LDH) levels [1]. The 5-year survival rate is ∼90% for AJCC stage I melanoma and ∼70% for AJCC stage II melanoma, but decreases significantly to 25–50% for AJCC stage III melanoma (depending on the number of lymph nodes involved), and ∼10% for stage IV disease [2]. Because the identification of metastatic disease is a major prognostic factor for melanoma recurrence and outcome, accurate staging of this disease is important for optimal management of these patients. The clinical and histopathological features cannot accurately predict the behavior of melanoma in all cases [3]. Therefore, a need exists for biomarkers which would help to identify patients at risk for disease progression, in addition to those individuals whose disease has already progressed subclinically [3].