In order to better understand the spatial distribution of thyroid vessels, a series of benign and malignant thyroid lesions were studied with three-dimensional (3D) histological stereomicroscopic reconstruction. Cases consisted of normal autoptic thyroids (n=6), colloid goitres (n=6), Basedow's disease (n=2), follicular adenoma (FA) (n=4) one of which with Hurthle cells (HC), minimally invasive, well-differentiated follicular carcinoma (FTC) (n=1), well-differentiated FTC with HC (n=1), poorly differentiated FTC (n=13) with extensive angioinvasion, papillary carcinoma (PTC) (n=8) and medullary carcinoma (MTC) (n=1). From each selected nodule, parallel sections were obtained for 3D reconstruction and for histological and immunohistochemical studies. In normal thyroid, large vessels were located at the periphery of the gland with smaller branches present within the thyroid parenchyma that encircled follicles. The same pattern of vascularisation is maintained in lesions showing a follicular architecture as colloid goitre, Basedow's disease, FA, well-differentiated FTC and the follicular variant of PTC. Neoplastic lesions, at variance with non-neoplastic lesions, contained rare anastomoses. Poorly differentiated FTC and MTC contained large intratumoural vessels surrounding avascular areas corresponding to solid neoplastic cellular sheets with necrosis. PTC were more vascularised and contained numerous vascular anastomoses. In conclusion, the present data indicate that the vascular distribution is related to the follicular, papillary or solid type of growth. Vascular anastomoses and intratumoural vessels surrounding solid avascular areas are signs of malignancy.