Angiogenesis (as microvascular density-MVD) and vascular endothelial growth factor (VEGF) expression were evaluated by immunohistochemistry in all types of human pre-invasive breast lesion, un-associated with invasive carcinoma, including florid ductal hyperplasia of usual type (FDHUT, 40 cases), atypical ductal hyperplasia (ADH, 10), well-differentiated intraductal carcinoma (WDIC, 16), intermediately differentiated intraductal carcinoma (IDIC, 25), poorly differentiated intraductal carcinoma (PDIC, 20), atypical lobular hyperplasia (ALH, 13), and lobular carcinoma in situ (LCIS, 12). Both parameters were also studied in normal glandular structures obtained from normal breasts or from breasts containing pre-invasive lesions. Increased vascularization was present in all lesion types (MVD mean values (expressed as vessel number/mm(2)): 115 +/- 8 in normal lobules, 146 +/- 26 in lesions; p < 0.05) and increased with lesion severity. In ductal lesions, MVDs were significantly higher in PDIC (190 +/- 65) and IDIC (167 +/- 61) than in FDHUT (123 +/- 40) and ADH (122 +/- 47); MVD was much higher in PDIC than in WDIC (p < 0.001). WDIC showed peculiar features, with a degree of vascularization closer to hyperplasia than to the other histological types of in situ ductal cancer; this observation is in line with the hypothesis that IDIC and PDIC may originate 'de novo', without a mandatory transition through WDIC. LCIS was more vascularized than ALH (168 +/- 50 and 125 +/- 40, respectively; p < 0.05), showing MVD values similar to those of PDIC and IDIC. The vascularization of normal lobules was constant, regardless of their association with lesions. VEGF expression in normal glandular structures was lower than in lesions, with the highest levels found in ductal lesions when compared with lobular lesions. No correlation was found between VEGF expression and the degree and/or type of vascularization.