In recent studies a new method has been proposed to detect circulating melanoma cells in the peripheral blood of patients, based on the amplification of the mRNA for tyrosinase, an enzyme involved in melanin biosynthesis that is expressed only by melanocytic cells. The sensitivity and clinical relevance of this method are still controversial. In the present study, 596 blood samples from 186 melanoma patients at various clinical tumour stages, together with samples from 25 healthy volunteers, were analysed with the aim of investigating the value of tyrosinase detection in predicting melanoma recurrence. We suggest a possible role for this marker in the monitoring of melanoma patients after the excision of regional lymph node metastases, and provide evidence that tyrosinase is related to the status of disease in advanced metastatic patients. Moreover, chemotherapy administration appeared to influence tyrosinase determination and may explain the discrepancies in the reported percentages of positive samples.