ObjectiveThe submandibular gland (SMG) is typically included in level I neck dissection specimens despite limited data demonstrating SMG invasion. The main objective of this article is to determine the rate and pathways of SMG invasion by squamous cell carcinoma of the oral cavity and oropharynx.Data SourcesA systematic review of relevant studies was performed, evaluating articles identified via the PubMed, Cochrane, and Medline databases.Review MethodsDescriptive features of primary tumors, primary treatment modalities, the rate and pathway of SMG invasion, and survival outcomes, if present, were reported following the PRISMA guidelines.ResultsThe initial literature search yielded 273 articles, of which 17 met inclusion criteria. A total of 2306 patients with 2792 SMG resections were analyzed. Fifty-eight resections (2.0%) were revealed to have tumor involvement. Among patients with SMG tumor involvement, the most common invasion pathway was direct SMG invasion by primary tumor (43 of 58, 74.1%). The second-most common mode of SMG invasion was from involved adjacent lymph nodes (10 of 58, 17.2%). Only 3 SMG resections out of 2792 (0.1%) had isolated metastatic parenchyma without evidence of direct tumor invasion or invasion by involved lymph nodes.ConclusionGiven this rarity of SMG involvement, preservation of SMG might be feasible in selected patient population. However, additional studies need to examine the functionality of preserved SMGs among patients who receive postoperative adjuvant radiation therapy.