In spite of the thyroid tissue heterogeneity, some biochemical and morphological features have been typically associated witb certain thyroid diseases. The aim of this study was to examime the ultrastructural cytochemical localization of thyroid peroxidase (TPO), TPO associated hydrogen peroxide generating sites (H2O2-sites) and monoamine oxidase (MAO), in relation with morphological characteristics and biochemical TPO activity in benign and malignant thyroid tissues. We analyzed 11 non-toxic multinodular goiter (MG), 5 Hashimoto´s thyroiditis (HT),  5 Graves´ disease (GD), 4 papillary carcinoma (PC), 1 oxyphilic (Hurthle) cell adenoma (OHCA) and 4 perinodular (PN) (normal) tissues obtained by surgery. Reaction for TPO (diarninobenzidine.DAB/H2O2), H2O2-sites (DAB without H2O2) and MAO (DAB/tyramine) was detected by electronic microscopy. TPO activitv (30000g) was measured (guaiacol,.G assay). In PN the TPO staining was seen in perinuclear cisternae, rough endoplasmic reticulum (RER) and some subapical vesicles but not in apical surface. In MG cells, a great TPO reaction heterogeneity was observed at similar locations than in PN, ranging from almost nule to strongly positive. TPO was absent at apical surface even in markedly stained cells. HT follicular cells showed TPO reaction in nuclear cisternae and the poorly developed RER. Some cells displayed TPO in largely dilated RER cisternae containing material resembling colloid. As a remarkable feature, Hurthle cells ffrom both HTand OHCA typically packed with mitochondria, showed clear TPO reaction in the prominent mitocohndria cristae but not in other organelles. In GD the nuclear cisternae, the enlarged RER cisternae and apical vesicles were strongly TPO positive. TPO was also seen at external surface of microvilli. PC tissues showed cellular atypism and no reaction for TPO. Positive H2O2-sites were observed in PN, MG, HT, GD and Hurthle cells awith the same localization and characteristics than TPO. MAO was positive in mitochondria of PN, MG and Hurthle cells. No MAO reaction was seen in GD and HT. Interestingly, MAO was intensely positive in nuclear cisternae of PC while mitochondria remained unreactive. TPO activitv was increased in MG and GD (mGU/mg protein; mean +/- SEM): PN 3.7+/-1.3,  MG 8.5 +/-4.5*, HT 6.4 +/- 3.9, GD 15.9 +/-5.2**, PC 2.4 +/-0. 6(*p<0 05**p<0 001 vs PN). In conclusion, the results indicate that the functionality of abnormal thyroid is associated with the proper TPO localization rather than TPO activity. In MG the absence of apical TPO agrees with the low-normal iodination despite a high TPO. H2O2-sites colocalize everywhere with TPO. The change of MAO distribution in PC should be considered as a potential feature of malignancy. The expression of thyroid differentiation parameters in non-malignant Hurthle cells is supported altbough the significance of unusual mitochondrial location is unknown.