Recent studies reported the possibility of detecting prostate adenocarcinoma and malignant melanoma cells in peripheral blood using RT-PCR of prostatic specific antigen (PSA), prostatic specific membrane antigen (PSMA) and Tyrosinase mRNAs. The PCR results showed high variability, ranging between 0% and 100% of positivity in patients with advanced disease. Our purpose was to evaluate the presence of tumor marker mRNAs in peripheral blood of prostate cancer and melanoma patients by means of RT-nested-PCR. We tested 70 and 36 peripheral blood samples from prostate carcinoma and malignant melanoma patients, respectively. The RT-PCR analysis showed the presence of PSA cDNA in 9 out of 70 (12.9%); PSMA cDNA in 14 out of 70 (20%); and Tyrosinase cDNA in 2 out of 36 (5.5%) peripheral blood samples from melanoma patients. Our study confirms the applicability of this sensitive method to monitor disease status. Although, the RT-nested-PCR of Tyrosinase is able to detect neoplastic cells in peripheral blood specimens, we suggest the necessity of a great caution in interpreting PCR results when the nested method has been used.