The distinction between endometrial hyperplasia and well-differentiated adenocarcinoma of the endometrium continues to be a difficult differential diagnosis in surgical pathology. Evidence-based diagnostic criteria for well-differentiated endometrial adenocarcinoma focus on histologic features that predict myoinvasion in the hysterectomy specimen. Only 2 diagnostic criteria with significant power aid in this distinction: complex glandular architectural patterns (glandular confluence, intraglandular complexity, and hierarchical papillary architecture) and marked cytologic atypia beyond that typically defined as atypical hyperplasia (ie, prominent macronucleoli visible at low power and marked nuclear pleomorphism). Application of these 2 criteria in problematic endometrial proliferations allows stratification of patients into 3 risk categories: very low risk (<0.05% risk of myoinvasion at hysterectomy)=complex atypical hyperplasia; intermediate risk (5.5% risk of myoinvasion at hysterectomy)=complex atypical hyperplasia, cannot exclude well-differentiated adenocarcinoma (borderline); and high risk (20% risk of myoinvasion at hysterectomy)=well-differentiated adenocarcinoma. In order to optimize the use of these diagnostic criteria, a variety of gland forming lesions that may mimic well-differentiated endometrioid adenocarcinoma must first be excluded. In addition, unusual morphologic patterns of low-grade endometrioid adenocarcinoma should be recognized, as they may cause confusion with other, higher grade (and therefore, more clinically aggressive) endometrial processes.