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Background This study characterized the infiltration of primary tumors along the intrinsic and extrinsic muscles of the tongue in oral tongue squamous cell carcinoma (OTSCC), to create a new surgical strategy that is suitable for most stages. A preliminary evaluation of this novel surgical approach was also conducted. Methods An anatomic study of macroscopic specimens from 10 human cadavers and 100 OTSCC patients was conducted. The anatomic characteristics of the primary tumors and the origin and distribution of fibers of the intrinsic and extrinsic tongue muscles were observed and measured. After initial treatment with curative intent, the 100 patients were regularly followed-up with clinical examination and imaging. Result Based on the anatomic characteristics of the primary tumors and tongue muscles, a new surgical approach was developed, and was described as muscle anatomy tongue surgery (MATS). MATS proved suitable for almost all stages of OTSCC. According to the morphology of the invasive tumor front, the 100 cases were divided into four types. The rate of 2-year local disease control was 98%, locoregional control 86%, disease-free survival 85%, and overall survival 89%. Tongue functions were perfectly recovered in more than 60% of the patients. Conclusion Application of the principles of MATS to the treatment of OTSCC proved suitable for almost all stages of the disease. MATS is a novel surgical technique that may improve outcomes in tongue cancer surgery. [ABSTRACT FROM AUTHOR]