Data reported in the literature about the clinical significance of tyrosinase expression in the peripheral blood of disease-free melanoma patients are still controversial. In the study described here, a review of the papers specifically addressing the evaluation of the relationship between sequential RT-PCR assays during follow-up and clinical evidence of disease progression was performed; data collected were reported in terms of sensitivity and specificity, together with the results obtained at our institutions. A total of 861 stage I to IV melanoma patients were included, from seven studies. The overall sensitivity was 61% (range 24-100%). The overall specificity was higher than the sensitivity (76.5%), with values ranging from 48 up to 90.9%; two of the studies with higher specificity values included only stage III patients. The highest sensitivity and the lower specificity values were associated with the highest number of tyrosinase determinations per patient. In conclusion, tyrosinase RT-PCR is a potentially useful molecular marker, at least in the follow-up of stage III disease-free patients, only if assays are repeated every 2 or 3 months. We suggest carrying out radiological procedures at least after the second consecutive positive determination, even in the absence of clinical symptoms.