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BACKGROUND: Sentinel node biopsy (SNB) for cN0 early squamous cell carcinoma (SCC) of the oral cavity has been validated by numerous studies. Around 30% of SNB will detect occult disease. Several clinical and morphological features of the primary tumor have been claimed to be predictive for occult metastasis in elective neck dissections. The aim of this study was to assess these factors in the context of SNB. METHODS: Seventy-eight patients undergoing SNB for T(1/2) oral SCC from the years 2000 to 2007 were prospectively included. Primary tumors were reviewed for the following morphological and clinical parameters: grade of differentiation, tumor depth, tumor thickness, perineural invasion, lymphatic invasion, vascular invasion, muscle invasion, lymphoplasmacytic infiltration, and mode of invasion, age, gender, primary tumor site, tumor side, and cT category. RESULTS: Statistical analysis revealed significance to predict occult metastasis in the SNB for grade of differentiation (P = 0.002), lymphatic invasion (P < 0.001), and mode of invasion (P < 0.001). None of the other factors reached significance. The mean tumor depth was 6.45 mm (range 0.72-15.15 mm) and the mean tumor thickness was 7.2 mm (range 0.72-15.15 mm). None of the cutoff values reached significance for predicting occult disease. CONCLUSIONS: Tumor depth and tumor thickness failed to achieve statistical significance for prediction of occult metastases in the context of SNB. Patients with cN0 early squamous cell carcinoma of the oral cavity should be offered SNB regardless of their tumor depth and thickness. Poorly differentiated carcinomas, carcinomas with lymphangiosis, and carcinomas with a dissolute mode of invasion show a high probability of positive SNB.