We applied quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to detect tissue-specific mRNAs in circulating cancer cells for the diagnosis of early-stage cancer. By Northern blotting, the thyroid peroxidase gene (TPO) was strictly expressed in the thyroid. We also used RT-PCR to examine TPO and thyroid stimulating hormone receptor (TSHR) mRNAs in peripheral blood in 33 thyroid papillary carcinoma patients at stages I (23 cases), II (8 cases) and III (3 cases), 49 noncancer patients with benign thyroid diseases, and 20 healthy volunteers. TPO mRNA was detected in 14 of 23 (61%) cases of stage I carcinoma but only 2 of 49 cases with benign thyroid disease. TPO mRNA was not detected in 20 healthy volunteers. By real-time quantitative RT-PCR, the estimated number of thyrocytes in the circulation ranged from 0.24 and 2700 cells per milliliter of whole blood in 7 of 9 patients at stages I and II, and thyrocyte number did not correlate with tumor size or serum thyroglobulin level. Our results might suggest that detection and quantification of tissue-specific mRNAs (e.g., TPO) in peripheral blood could serve as a means to identify potential tumor markers at early stages of cancer.