Adenosarcoma (AS) is a rare biphasic neoplasm of the female genital tract characterized by an admixture of benign glandular and low-grade mesenchymal components. The classic low-power growth pattern is periglandular stromal proliferation accompanied by a variable degree of cytologic atypia and mitotic activity. However, as cytologic atypia is an objective criterion, and the number of mitotic figures required for diagnosis is inversely proportional to stromal cytologic atypia, there is a relatively wide variation in the decisive factors used among pathologists to diagnose an AS. Furthermore, the exact number of microscopic fields sufficient for diagnosis and/or the size of the fields adjusted to a specific microscope are not well established. These uncertainties are still an occasional source of misclassification of AS. Our study was conducted to explore the role of immunohistochemistry in the diagnosis of AS. Eight ASs were retrieved and compared with 14 endometrial polyps and 14 atypical polypoid adenomyomas. Immunohistochemical stains for Ki-67, caldesmon, smooth muscle actin, desmin, and CD10 were performed on all cases. All AS had a polypoid growth pattern with a variable increase in periglandular stromal cellularity and stromal nuclear atypia. The mitotic activity ranged from 1 to 15/10 high-power fields, and all AS demonstrated a distinct increase in Ki-67-positive nuclei in the periglandular zone compared with the adjacent stroma, regardless of the mitotic count. The Ki-67-labeling index in periglandular zones was ∼20% compared with <5% in the adjacent stroma. This zonation was not observed in any case of atypical polypoid adenomyomas or endometrial polyps. None of the other stains (CD10, smooth muscle actin, desmin, and caldesmon) helped to differentiate between these entities. Thus, characteristic zonation by Ki-67-staining pattern is a helpful adjunct to the routine morphology in the diagnosis of AS, particularly in curettage specimens, which may lack some of the classic morphologic diagnostic features.