<h3>Background</h3> Osteosarcoma is the most common primary bone tumor, with 10% of cases affecting the head and neck. Demographics of head and neck osteosarcoma are different from those elsewhere in the musculoskeletal system. Prognosis is strongly dependent on negative resection margins with the use of neoadjuvant chemoradiotherapy in select cases. <h3>Description</h3> We present a case of a 58-year-old male nonsmoker patient who presented with a lump in his left upper jaw. Clinical examination revealed an exophytic mass in the upper left tuberosity of the maxilla suspicious for squamous cell carcinoma with no associated lymphadenopathy. <h3>Findings</h3> Radiological investigations revealed a metabolically active left maxillary lesion with destruction of the maxillary sinus. Histologic examination of a superficial biopsy initially suggested a proliferative fibro-osseous lesion; however, a second deeper biopsy was diagnostic of osteosarcoma, and the patient was referred to a sarcoma center. Immunohistochemistry showed AE1/AE3 and CK(MNF.116) positivity in occasional cells with a Ki67 proliferation index of 60%. This was diagnostic of grade 2-3 osteosarcoma. Multidisciplinary management of the patient included neoadjuvant chemotherapy and total maxillectomy and dental prosthetic rehabilitation. The patient is still under follow-up. <h3>Conclusions</h3> This case of primary osteosarcoma of the maxilla is rare and scarcely reported in the literature. Clinical differential diagnoses include squamous cell carcinoma, and histologic differential diagnosis includes fibro-osseous proliferative lesions in undersampled cases. It is important to consider osteosarcoma in destructive lesions, as it requires prompt and early specialist intervention to maximize the chances of negative surgical margins, which is the mainstay of treatment for this disease for prognosis.