It is believed that qualitative changes in thyroid peroxidase (TPO) cause decreased enzyme activity in differentiated thyroid carcinoma. To re-evaluate TPO expression in thyroid cancer, TPO mRNA expression was compared with TPO protein expression in 38 samples of thyroid tissue obtained from patients with various thyroid diseases. In Northern blot studies, while TPO mRNA was highly expressed in tissues from all 18 benign lesions, it was strongly suppressed in 14 tumours, including 12 out of 12 papillary carcinomas, one of seven follicular carcinomas, and one medullary carcinoma. TPO mRNA was not detected in six carcinomas, of which four were papillary, one follicular, and one medullary, by the usual Northern blot method. The 14 cases with strong underexpression of TPO mRNA were very weakly stained with anti-TPO monoclonal antibody 38E, whereas all 18 benign tissues were strongly stained. Moreover, a comparative study of TPO expression by Northern blot and immunohistochemical analysis revealed a positive correlation between TPO mRNA expression and the staining intensity of TPO protein. These results suggest that strong suppression of TPO mRNA transcription causes low TPO activity in papillary carcinoma; immunohistochemical loss of TPO may be a useful diagnostic marker. TPO mRNA expression in differentiated thyroid carcinomas did not always correlate with the mRNA expression of thyroglobulin, thyroid stimulating hormone receptor, and thyroid transcription factor 1.