Sentinel lymph node (SLN) sampling may provide staging information without exposing patients to risks of lymph node dissection. There is no consensus protocol for optimal pathologic handling of these specimens. This study compares 2 ultrastaging protocols of SLN in endometrial carcinoma (EC). All SLN were serially sectioned perpendicular to the long axis in 2 mm intervals and entirely submitted for routine hematoxylin and eosin (H&E) processing. SLN negative by routine processing had ultrastaging (US) by one of the following: method 1 (M1), 5 H&E levels at 250 μm intervals with 2 unstained slides at each level; pankeratin immunohistochemistry (IHC) performed on level 1 in cases with negative H&E levels or method 2 (M2), 1 H&E level + 2 unstained slides cut 250 μm into the tissue block; pankeratin IHC performed in cases with negative H&E. Histologic subtype, numbers of SLN, positive SLN, non-SLN, positive non-SLN, and metastasis size were recorded. A total of 178 patients had 527 SLNs (1-16 per case; median, 2 SLN) sampled during hysterectomy for the following EC histotypes: endometrioid International Federation of Gynecology and Obstetrics grade 1/2, 117 (66%); endometrioid International Federation of Gynecology and Obstetrics grade 3, 18 (10%); serous, 20 (11%); carcinosarcoma, 11 (6%); clear cell, 9 (5%); and undifferentiated, 3 (2%). In all, 172 patients had ultrastaging: M1=65; M2=58. In total, 33 patients were SLN positive. Twenty-seven had SLN submitted for US: M1=11; M2=16. Eleven patients had additional SLN detected by US: M1=5; M2=6. Of these, 8 were patients whose SLN were only detected by US representing an increase of 32% in number of patients with positive SLN. Six patients (M1=2; M2=4) with negative SLN had a positive non-SLN. Mean size of ultrastage-detected metastasis was 0.24 mm for M1 and 0.38 mm for M2. Statistical analysis comparing M1 and M2 detected no statistically significant associations with respect to number of positive SLN detected, size of metastasis or false-negative rate and method. The methods performed similarly for both low-grade and high-grade EC. A more comprehensive US protocol had no significant advantages over a single wide interval and IHC in this study population. A pankeratin IHC stain enhances metastasis detection. Additional studies are required to further test this limited protocol as well as to evaluate the clinical significance of the low volume disease detected by ultrastaging.