The occurrence, structure and extent of microvascular density were examined in normal endometria, hyperplasia of different types and adenocarcinomas of different degrees of differentiation to determine their biologic and clinical significance in tumor development and progression. Computer-assisted quantitative image analysis was carried out on 12,500 vessels in regard to vessel number, vessel volume, size, shape and extent of vessel antibody staining, with sensitivity and reproducibility exceeding 99%. The results showed the extent, pattern and characteristics of microvascular density to be intimately associated with extent of tumor development and degree of differentiation of the tumor. Vessel number increased with superficial location in normal endometrium, with increased degree of hyperplasia and atypia and with increased degree of dedifferentiation of adenocarcinoma. Increased vessel shape alterations were characteristic of atypical complex hyperplasia when compared to other types of hyperplasia. Vessel number, size and shape were similar in proliferative endometrium and simplex type hyperplasia, and microvascular density in atypical complex hyperplasia was similar to that in well-differentiated adenocarcinoma. The results indicated that vessel shape alterations occur during progression of hyperplasia and vessel size increase occurs in complex-type hyperplasia and in moderately differentiated adenocarcinomas. We conclude that microvascular density is associated with endometrial location and with specific patterns of alteration in different stages of endometrial disease. The results suggest potential clinical applications of vessel analysis for determination of clinical behavior of endometrial preneoplastic and neoplastic alterations. ' 2005 Wiley-Liss, Inc.