Background: Epidermal growth factor receptor (EGFR) mutations exist in patients with oral cavity squamous cell carcinoma (OSCC), but few data about mutation patterns with clinical outcomes were reported. +Methods: Fifty-six formalin-fixed paraffin-embedded tumor samples were obtained surgically from OSCC patients. Direct sequencing of EGFR was carried out using nested polymerase chain reaction. The relationship between EGFR status and clinical courses was analyzed. +Results: Two (3.56%) missense mutations (G857R; L862Q) in exon 20 were identified. Two types of silent mutation, A859A in exon 21 (1.79%) and Q787Q mutations in exon 20 (30.36%), were also found. No mutation was detected in exons 18 and 19. No significant difference in disease-free survival and locoregional control rate was shown between patients with and without Q787Q mutation. +Conclusions: We identified a high frequency of Q787Q mutation and a less prevalent active EGFR mutation in OSCC patients in Taiwan where betel nut is commonly chewed.