Detection of circulating melanoma cells by reverse transcriptase – polymerase chain reaction (RT-PCR) is a molecular diagnostic procedure which is used to predict prognosis in melanoma patients. The most widely used specific marker for detection of circulating melanoma cells by RT-PCR is expression of tyrosinase gene. This procedure has shown high specificity and low threshold for detection of melanoma cells. Most of the studies have shown that prognosis is worse in patients in which circulating melanoma cells were detected. Detection of circulating melanoma cells has been studied also as a marker for predicting response to therapy. The clinical value of this procedure is limited by the proportion of patients with clinically confirmed distant metastases being tyrosinase negative in almost all the studies. Studies have shown that analysis of additional markers to tyrosinase enables detection of circulating melanoma cells in a higher percentage of melanoma patients. RT-PCR has shown a lower threshold for detection than other methods (immunohistochemistry) in detection of melanoma metastases in lymph nodes.