Oral tongue squamous cell carcinomas (OTSCC) have a poor prognosis compared with other head and neck cancer subsites. Therefore novel therapies are required for patients with recurrent or metastatic OTSCC. Fibroblast Growth Factor Receptor 1 (FGFR1) amplification frequently occurs in squamous cell carcinoma of the lung and represents a novel druggable therapeutic target. The present study examined the frequency and clinical associations of FGFR1 amplification in a cohort of 123 OTSCC patients. Fluorescence in situ hybridization assay was used to determine amplification of the FGFR1 gene which was defined as >50% of cells displaying ≥5 copies of the FGFR1 signal, or a FGFR1/chromosome 8 ratio >2. FGFR1 gene amplification was present in 10/107 (9.3%) cases and was significantly associated with smoking status (P=0.03) with 10/74 (13.5%) smokers being FGFR1 amplified compared to 0/31 (0%) non-smokers. We also found that 9/10 (90%) of the FGFR1 amplified patients were male, compared to only 63/97 (65%) of the non-amplified patients, though this difference failed to reach statistical significance (P=0.16). There were no associations with age, stage, T stage, nodal status, alcohol history or performance status (all P>0.05). Outcome was not significantly different between FGFR1 amplified and non-amplified patients. We have shown that FGFR1 amplification is a frequent event in OTSCC with approximately 10% of cases showing amplification of the gene, which may define a population of patients who could benefit from targeted therapeutic treatment with novel FGFR1 inhibitors. Furthermore, smokers with OTSCC may represent a population enriched for this molecular phenotype. We propose that further investigation of FGFR1 amplification in other head and neck cancer subsites is warranted to fully determine the frequency of amplification of this targetable oncogene in head and neck squamous cell cancer.