BackgroundMetastatic lymph node involvement influences therapy decisions and serves as a prognostic indicator in oral squamous cell carcinoma (OSCC). However, many early‐stage patients with clinically negative lymph nodes exhibit no metastasis upon surgical staging. This study aimed to identify differentially expressed miRNAs capable of distinguishing pathologically positive (pN+) from negative (pN0) nodes in OSCC patients without clinical evidence of lymph node metastases (cN0).MethodsExpression levels of 798 miRNAs were assessed in tumor samples from 10 pN+ and 10 pN0 patients using the Nanostring nCounter platform. Validation was performed in an independent cohort of 15 pN+ and 24 pN0 patients through RT‐qPCR.ResultsEight miRNAs exhibited differential expression between pN0 and pN+ patients. Notably, hsa‐miR‐99a‐5p demonstrated high sensitivity and specificity in predicting patients at higher risk of positive lymph nodes.ConclusionsThese findings highlight hsa‐miR‐99a‐5p as a potential biomarker for detecting lymph node metastasis in primary OSCC tumors.