Abstract Context.—Endometrial tissue specimens are commonly encountered in daily practice. It is well known that a number of problematic diagnostic scenarios occur relative to these specimens. Objective.—To emphasize practical aspects of endometrial specimen handling and reporting, with selected comments on common diagnostic pitfalls, including (1) the diagnosis of endometrial intraepithelial carcinoma in atrophic endometrial biopsy specimens, (2) evaluation of adequacy of endometrial sampling specimens, (3) problems in diagnosing and measuring the depth of myometrial invasion in endometrial carcinoma, (4) the question of metastasis versus independent primaries in concurrent carcinomas of endometrium and one or both ovaries, (5) the problematic differential diagnoses between type 1 (primarily endometrioid) and type 2 (primarily serous) adenocarcinomas, and (6) atypical hyperplasia and proposed classification systems for its replacement. Data Sources.—Published literature, consensus statements, and personal experience. Conclusions.—A systematic approach to the handling and reporting of endometrial specimens reduces the potential for omission and error. Recognition of diagnostic pitfalls and practical approaches to their resolution help improve quality.