Until recently, the histologic diagnosis of obstetrical and gynecologic neoplasia was based principally on morphologic criteria. However, interobserver reproducibility for entities such as squamous intraepithelial, endometrial, and trophoblastic disease varies widely between observers. This inherent variability in interpretation between individuals has led to wide ranges in diagnostic precision between practices, and in many cases, between recognized experts. The advent of immunohistochemistry, and the more recent accelerated discovery of new genes and their functions has resulted in the discovery of cellular proteins or nucleic acids that are differentially expressed in tumors. When applied in conjunction with existing histologic criteria, these "biomarkers" have the potential to enhance diagnostic consistency and reproducibility. The gains expected are to practicing diagnostic pathologists (who will enjoy greater diagnostic consistency) and to academics (for whom biomarkers may uncover new pathways unappreciated by histologic diagnosis alone). However, fundamental to the success in both arenas will be critical analysis of the potential pitfalls in immunohistochemistry, strict validation of new markers as they arrive in the field, and a realistic view of their value in the laboratory management of obstetrical and gynecologic diseases.