INTRODUCTION AND IMPORTANCE: Odontogenic myxoma (OM) is an infrequent benign mesenchymal odontogenic tumor of the jaws composed of rounded and angular cells dispersed in an abundant mucoid stroma. An aggressive and vascularized presentation is unusual. CASE PRESENTATION: A 68-year-old woman was evaluated for a mass located under the palate and extended to the cheek. A large flattened mass covered the entire palate, except the left lateral dental arch, and extended to the cheek as a firmed 6 × 6 × 5 cm mass. An enhancement computed tomography and a magnetic resonance imaging revealed a large, heterogenous, expansive, 80 × 64 × 58 mm mass that destroyed the right maxilla and extended to the soft tissues of the cheek. Minimally invasive endovascular angiography and embolization was performed preoperatively. Through a modified Weber-Ferguson incision, a partial right lateral maxillectomy was performed, conserving the right nasal fossa and a left canine tooth, medially, and the floor of the orbit, upward. Pathology study reported an odontogenic myxoma with compromised margins but reexcision margins were negative. One year after surgery, there is no evidence of disease. CLINICAL DISCUSSION: Pathological and radiological differential diagnosis that includes a large number of benign and malignant lesions are discussed. All authors agree that wide surgical excision is the treatment of choice. CONCLUSIONS: Wide excision resulted in good functional and local control. Preoperative embolization is needed in case of a vascularized lesion. No immediate surgical reconstruction should be recommended to facilitate clinical surveillance and early recurrence detection.