The buccal mucosa is the site with the highest risk of contracting a malignancy in habitual betel quid chewers who expose the buccal mucosa to high doses of carcinogens. Of all oral cancers, those of the buccal mucosa are associated with the poorest prognoses. Therefore, it would be helpful to have an animal model to evaluate new treatment modalities for buccal mucosa cancer. In the present study, we evaluated whether the imprinting control region (ICR) mouse animal model could be employed as a cancer model for buccal mucosa cancer. Sixty male ICR mice were randomly divided into two groups, a normal group (n=10) and a cancer-induced group (n=50). Each mouse in the cancer group was inoculated with 0.05 ml U14 cancer cell suspension (1x107/ml) on the buccal mucosa. Histological staining and gene expression assays revealed that neck lymph node metastasis animal models were established. After 20 days, the cheek tumor formation rate of the ICR mice reached 100%. Furthermore, the neck lymph node metastasis rate was 53%. We identified that U14 cells produce strong metastasis in ICR mice. Metastasis of the tumor to the lymph node began with carcinoma metastasis encroaching on the marginal sinus. Then it infiltrated to the cortex and medulla and the infiltration continued until the normal lymph node structure was completely damaged. This animal model may be employed in medical research on buccal mucosa cancer and cervical lymph node metastasis. In conclusion, our findings indicate that U14 cell-induced mouse buccal mucosa cancer may be a potential cancer model for human buccal mucosa squamous cell carcinoma.