Accurate diagnostic of metastasis in regional lymph nodes of patients with oral squamous cell carcinoma (OSCC) is important in treatment choice and patient’s prognosis. Clinical staging through physical exam and imaging techniques is inefficient in detecting occult metastasis, thus elective neck dissection is usually the treatment of choice for high risk cases. However, although improving locoregional control, it represents over-treatment for a substantial proportion of patients, impacting in their quality of life. The pathologic evaluation of resected lymph nodes through H&E is not sensitive in detecting small metastatic deposits, not accurately selecting patients that would benefit from adjuvant therapies and contributing to an increased risk of progression to a potentially incurable disease. Step-sectioning followed by immunohistochemistry is more accurate but more time-consuming, delaying adjuvant therapies. Finding more accurate diagnostic markers may improve locoregional control, treatment response and overall survival of OSSC patients. MicroRNAs are promising diagnostic markers mostly for having tissue-specific expression. This study aimed to find microRNAs able to detect metastatic cells in a background of lymphoid tissue.Four microRNAs were evaluated by qRT-PCR in 100 lymph nodes from 48 patients. Pathological examination through H&E and immunohistochemistry classified lymph nodes as positive (18 macrometastasis, 5 micrometastasis and 2 isolated tumor cells) and metastasis-free (n=75).The concordance between molecular and pathology results ranged from 76% to 100%. Markers showed an accuracy ranging from 84.2% to 100%, positive predictive values of 100%, negative predictive values between 84.2% and 100%, and AUC between 0.92 and 1.0.MicroRNA expression showed to be specific, sensitive and accurate as diagnostic markers of cervical metastasis in OSCC patients. Further analyses using different approaches at different time-points during patients’ diagnostic and treatment, might confirm the usefulness of these markers as tools to aid surgeons in the best management of OSCC patients.