Background: Neck management for cN0 neck remains controversial for T1-2 oral tongue and buccal squamous cell carcinoma (SCC). Increased tumor thickness and perineural invasion (PNI) are two pathologic features that correlated with cervical lymph node (LN) metastasis and poor survival. However, the relationships between these two features remain unclear. Methods: Detailed histologic reevaluation under hematoxylin and eosin staining was performed in tumors of 212 consecutive patients with T1-2, cN0 oral tongue and buccal SCC. The interrelationships between the impacts of tumor thickness and PNI on cervical LN metastasis and disease-specific survival (DSS) were analyzed. Results: Increased tumor thickness (>6 mm) correlated with higher LN metastasis and poor 5-year DSS rates in univariate analysis. However, only PNI independently predicted both in multivariate analysis (P = 0.004 and P = 0.039, respectively). When stratified by PNI status, increased tumor thickness did not correlate with higher LN metastasis rate in either PNI-negative or PNI-positive groups (P = 0.337 and P = 0.730). Compared to patients with thin tumors (≤6 mm), patient with thick tumors revealed significantly higher LN metastasis rate (41.9 vs. 16.4 %, P = 0.001) and lower 5-year DSS rate (77.5 vs. 93.7 %, P = 0.006) only at the presence of PNI. Conclusions: PNI can be a major determinant for higher LN metastasis and poor 5-year DSS rates associated with increased tumor thickness in T1-2 oral tongue and buccal SCC. Careful evaluation of PNI should be mandatory in routine pathologic examination, aside from the measurement of tumor thickness.