Testing of tumor tissue remains the recommended method for detecting the 
presence of somatic mutations in human malignancies. V600E is the most frequent 
somatic point mutation in metastatic melanoma, providing a unique molecular 
marker for this malignancy. In addition, tumors carrying this mutation are 
primary candidates for BRAF-targeted therapy. Although metastatic melanoma 
patients usually have sufficient tumor tissue available for genetic analyses, 
the detection of V600E in blood can have prognostic and predictive value. In 
addition, patients are rarely re-biopsied and genetic testing in blood can be 
useful for monitoring response to therapy. Cell-free DNA (cfDNA) and cell-free 
RNA (cfRNA), RNA associated to platelets and circulating tumor cells (CTCs) are 
some of the materials that can be derived from the blood of cancer patients. 
cfDNA can be easily purified from serum and plasma and contains DNA fragments of 
tumor origin. For this reason, it is the most widely used material for the 
detection of somatic mutations in blood. Several methodologies have been used to 
determine V600E status in the cfDNA of metastatic melanoma and some studies have 
demonstrated that the identification and follow-up of V600E in cfDNA can have 
prognostic and predictive value.