Background: maxillary bone invasion (MBI) is not uncommon in hard palate or upper alveolus (HP/UA) cancer; however, there have been relatively few reports about the MBI of HP/UA cancer. Patients and Methods: this was a multi-center retrospective study, enrolling 144 cases of HP/UA cancer. MBI was defined by surgical pathology or radiology follow-up. The multiple prediction models for MBI were developed in total cases and in cases having primary bone resection, using clinical and radiological variables. Results: computerized tomography (CT) alone predicted MBI, with an area under receiver operating curve (AUC) of 0.779 (95% confidence interval (CI) = 0.712–0.847). The AUC was increased in a model that combined tumor dimensions and clinical factors (male sex and nodal metastasis) (0.854 (95%CI = 0.790–0.918)). In patients who underwent 18fluorodeoxyglucose positron emission tomography/CT (PET/CT), the discrimination performance of a model including the maximal standardized uptake value (SUVmax) had an AUC of 0.911 (95%CI = 0.847–0.975). The scoring system using CT finding, tumor dimension, and clinical factors, with/without PET/CT SUVmax clearly distinguished low-, intermediate-, and high-risk groups for MBI. Conclusion: using information from CT, tumor dimension, clinical factors, and the SUVmax value, the MBI of HP/UA cancer can be predicted with a relatively high discrimination performance.