Background: The prognostic significance of various histopathologic lymph node-based biomarkers in oral squamous cell carcinoma (OSCC) needs further evaluation. Methods: Retrospective analysis of 212 OSCC patients with regional metastasis to determine the association of extranodal extension (ENE), extent of ENE, size of metastatic deposit, lymph node yield (LNY), lymph node ratio (LNR), and topography of involvement with survival outcomes. Results: The presence of ENE, larger nodal deposit, higher pN stage, lymph nodes in the lower levels, and patients who did not receive adjuvant treatment had poor disease-free survival (DFS). In addition, more positive nodes and high LNR showed worse overall survival (OS). ENE beyond 5 mm resulted in poorer outcomes. Larger sizes of metastatic deposit predisposed to ENE. Multivariate analyses showed only lower level of neck involvement to affect both DFS and OS. Conclusions: Lymph node metastasis to lower levels and other lymph node characteristics affect prognosis and must be considered in the evolution of staging systems for OSCC.