AbstractA number of specific genes encoding for melanosomal proteins are selectively expressed in melanocytes and melanomas. For detection of circulating melanoma cells, the expression of the tyrosinase gene is most widely used. Several cohorts of melanoma patients from single institutions have been analyzed by various research groups for the presence of circulating melanoma cells in all stages of disease. The percentage of patients with evidence of occult tumor dissemination has been correlated with stage of disease in several, but not all, reports. Two prospective analyses suggest that the PCR result is of prognostic value in melanoma. Several laboratories have found PCR evidence for circulating melanoma cells in the vast majority of untreated patients with stage IV disease, although other groups have reported much lower frequencies. Taken together, there is a wide range of results. Methodological differences likely account for this discrepancy. With the availability of true quantitative RT‐PCR systems, such as the Light Cycler system, accurate quantification of tyrosinase transcripts over a range of 1–10,000 tumor cells per ml of blood is possible. Quantitative RT‐PCR systems also dramatically improve quality control, since exact quantitation of housekeeping gene mRNA facilitates determination of sample quality. Semin. Surg. Oncol. 20:319–328, 2001. © 2001 Wiley‐Liss, Inc.