Malignant melanoma is the most common cause of death from skin cancer. Wide surgical excision of localized melanoma in its primary stages remains the main curative therapy. Identifying patients at an early tumour stage is therefore one of the most significant steps for treatment. In the last decades, molecular pathology rapidly established itself in melanoma research. We present new molecular methods, their significance and their application, especially focusing on BRAF( V600) mutation and BRAF-inhibiting tumor targeting therapy. Resistance to tumor targeting therapies and cell line experiments, which have evidenced a sub population with stem cell properties, illustrate melanoma heterogeneity. Efforts to develop drugs that target more than a single target gene are currently underway.