AbstractBackgroundSentinel lymph node biopsy (SLNB) is used to improve the staging of and guide treatment in patients with early‐stage T1–T2 N0 oral squamous cell carcinoma (OSCC). The role of sentinel nodes (SNs) and the use of SN‐technique in advanced OSCC (T3–T4 and/or N+) remain to be evaluated. This study investigates the nodal drainage and the rate of positive SNs (SNs+) in all stages of OSCC.Materials and MethodsIn total, 85 patients with T1–T4 OSCC diagnosed 2019–2021 were included. We used a prolonged interval between peritumoral injection of radionuclide and SPECT–CT to include all SNs.ResultsPatients with advanced OSCC presented a higher proportion of contralateral lymphatic drainage and a higher rate of SN+ compared to patients with early‐stage disease. T3–T4 and N+ tumors presented a tendency for a higher rate of contralateral lymphatic drainage compared to T1–T2 and N0 tumors (p= 0.1). The prevalence of positive nodes (SNs+) was higher among patients with advanced disease, T3–T4 versus T1–T2 (p= 0.0398).ConclusionSN‐assisted ND enables identification and removal of all SNs + and has the potential for more accurate staging and could possibly give prognostic advantages regarding regional recurrence for all OSCC patients, especially among those with advanced disease. The precise localization of the SNs + also suggests that a more individualized ND approach might be possible in the future even for patients with advanced OSCC.