Frozen section and intraoperative imprint cytology (IIC N ) are 2 methods used for intraoperative pathologic assessment of sentinel lymph nodes (SLNs). The SLN evaluation of patients with invasive lobular carcinoma (ILC) results in a relatively high number of false-negative results using either of these methods. The purpose of this study was to evaluate the added benefits that intraoperative immunohistochemical-cytokeratin staining (I CK-IHC ) can bring to IIC N in the evaluation of SLN in patients with ILC. A total of 59 breast cancer patients with ILC underwent an SLN biopsy evaluated by our standard IIC N assessment in addition to I CK-IHC . The results of IIC N with I CK-IHC were compared with the final histopathologic assessment consisting of standard hematoxylin and eosin staining and additional cytokeratin staining of nodes. Intraoperative evaluation of SLN using IIC N and I CK-IHC correctly diagnosed the nodal status in 45 of 59 (76.3%) patients. On final histopathologic assessment, 31 of 59 (52.5%) patients were found to have positive nodes. Using I CK-IHC , 17 of these 31 positive cases (54.8%) were detected.Using IIC N alone, without the benefit of I CK-IHC , only 13 of 31 (41.9%) positive cases were detected intraoperatively. For patients with ILC, I CK-IHC staining in addition to IIC N improves accuracy over using IIC N alone. In this study, I CK-IHC staining demonstrated a 12.9% improvement in the detection of SLN metastases in patients with ILC. Cytopathologists should consider employing I CK-IHC staining to evaluate the touch-imprint slides of SLN in ILC patients.