Abstract: Objective: To assess the significance of sentinel lymph node biopsy (SLNB), serial sectioning and cytokeratin immunohistochemical staining in the diagnosis and staging of Stage- cN0 oral squamous cell carcinoma (OSCC). Methods: Paten blue stain of sentinel lymph nodes (SLNs), 99mTc-dextran SPECT lymphoscintigraphy and intraoperative γ - ray probes were used to examine the SLNs in 31 cases with Stage- cN0 oral cancer. H&E staining and a cytokeratin AE1/AE3 immunohistochemistry(IHC) assessment, with serial sections, were conducted in addition to a routine pathological examination of lymph nodes. The value of the routine pathological examination of the SLNs, serial sections and IHCdetermination for cervical lymph node metastasis of Stage- cN0 OSCC was appraised. Results: A total of 45, 55 and 51 SLNs were detected in 25 (80%), 31 (100%) and 30 (96.5%) of the cases through use of the blue stain, γ - ray probes, and SPECT lymphoscintigraphy, respectively. The average SLNs found in each case of the groups was 1.4 (1 to 3) and there were 1302 non- SLNs. Six positive SLN metastases were detected by routine pathological examination, among which 1 case was found to be an accompanied positive metastasis of non- SLN. One positive SLN metastasis was found after examination of serial sections plus routine H&E staining and 2 were detected using serial sections plus AE3 immunohisto-chemical staining methods. No positive non- SLNs were found in the study. Conclusion: In order to make more progress in accurate SLNB diagnosis, serial sections and IHC (AE1/AE3) methods can be used to screen for micrometastases which are difficult to identify by routine pathological sections and H&E staining alone.