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OBJECTIVES: The aims were to assess the technical feasibility of sentinel node biopsy (SNB), to validate SNB against elective neck dissection, and to report the results of the clinical application of the SNB concept for early oral and oropharyngeal squamous cell carcinoma. STUDY DESIGN: Prospective consecutive cohort analysis. METHODS: Between 2000 and 2006, a total of 79 patients were included. Lymphatic mapping consisted of preoperative lymphoscintigraphy and intraoperative use of a hand-held gammaprobe. Twenty-eight patients were assessed for feasibility and validation; the SNB was done in context with an elective neck dissection. Fifty-one patients were evaluated in an observational trial; elective neck dissection was performed only in case of positive SNB. RESULTS: Validation revealed a sentinel node detection rate by lymphoscintigraphy of 93%, with the gammaprobe of 100%. The negative predictive value of a negative SNB was 100%. During the observational trial 40% of the patients were upstaged as a result of a positive SNB. Intraoperative frozen section analysis showed a negative predictive value of 83%. Two patients (6%) with negative SNB experienced a neck recurrence, the negative predictive value of SNB was therefore 94%. Patients with positive SNB were treated successfully with elective neck dissection. CONCLUSIONS: SNB is technically feasible and reproducible with a high sentinel node detection rate. Validation against elective neck dissection revealed a negative predictive value of 100%. Application of the SNB concept in clinical practice was very successful. The recurrence rate within the neck was very low and the morbidity and cost of an elective neck dissection could be spared to 60% of the patients.