Melanoma is the leading cause of death from skin cancer in industrialized countries. Clinical and histological variables such as primary tumor invasion, ulceration, and lymph node status might fail to identify early-stage disease that will eventually progress. Tumor biomarkers might help to identify patients with early-stage melanoma who are likely to develop advanced disease and would benefit from additional therapies. These biomarkers offer the possibility of improved tumor staging through the molecular detection of microscopic lymph node metastases that are not visible on routine histological examination. We focus on biomarkers localized to the tumor tissue and those of prognostic value. We give an overview of the melanoma biomarkers that are most helpful for prediction of patients' outcomes, and discuss the primary melanoma biomarkers that have been shown to be of prognostic significance independent of primary tumor thickness and other common clinical prognostic indicators. Although such tumor-associated biomarkers are thought to have the greatest potential, a lack of reliable data makes their true clinical utility difficult to determine. We conclude that several biomarkers show promise in early studies; however, additional large-scale studies are warranted. We suggest cautious optimism for the field of melanoma biomarkers, which we expect to be translated into clinical practice over the next few years.