Squamous cell carcinoma of the oral cavity (SCCOC) is one of the most prevalent tumors of the head and neck region. Despite improvements in treatment, the survival of patients with SCCOC has not significantly improved over the past several decades. Most frequently, treatment failure takes the form of local and regional recurrences, but as disease control in these areas improves, SCCOC treatment failures more commonly occur as distant metastasis. The presence of cervical lymph node metastasis is the most reliable adverse prognostic factor in patients with SCCOC, and extracapsular spread (ECS) of cervical lymph nodes metastasis is a particularly reliable predictor of regional and distant recurrence and death from disease. Decisions regarding elective and therapeutic management of cervical lymph node metastases are made mainly on clinical grounds as we cannot always predict cervical lymph node metastasis from the size and extent of invasion of the primary tumors. Therefore the treatment of the neck disease in the management of SCCOC remains controversial. The promise of using biomarker-based treatment decisions has yet to be fully realized due to our poor understanding of the mechanisms of regional and distant metastases of SCCOC. We will summarize the current status of investigations into SCCOC metastases and potential of these studies to impact basic research investigators and clinicians confronting SCCOC in the future.