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To evaluate the occurrence and prognostic significance of perineural invasion (PNI) in squamous cell carcinomas (SCC) of the oral cavity and oropharynx.A retrospective study of 101 patients with previously untreated SCC of the oral cavity and oropharynx was undertaken to evaluate the occurrence and prognostic significance of PNI in relation to local recurrence, regional recurrence, distant metastasis and survival. The logistic regression test was used for univariate and multivariate analyses. Actuarial survival curves were determined using the Kaplan-Meier method.PNI was present in 26 (25.7%) of 101 patients and was significantly associated with tumor differentiation, lymph node metastasis, and depth of invasion. Univariate analyses showed PNI was associated with local recurrence (P = .005), regional recurrence (P = .007), and distant metastasis (P = .013). In multivariate analysis, PNI was significantly associated with regional recurrence (P = .033) and distant metastasis (P = .021), but not with local recurrence (P = .109). The 5-year disease-specific survival for patients with and without PNI was 56.6% and 94.6%, respectively (P < .0001).PNI is an important predictor for outcome of patients with SCC of the oral cavity and oropharynx.