Acute myeloid leukemia (AML) is an aggressive hematological malignancy due to genetic alterations characterized by an overproduction of neoplastic clonal myeloid stem cells in both the bone marrow and peripheral blood. We report a case of a 43-year-old man referred to the department of hematology with a three-week history of palatal pain and weakness. The physical examination revealed an ecchymosis on the left hard palatal mucosa and necrosis. The maxillofacial computerized tomography (CT) scan revealed large osteolysis of the left maxillary bone and a fistulated soft palate. The lesion's biopsy showed an acute polymorphic inflammation with no sign of malignancy. Laboratory findings revealed anemia, thrombocytopenia, elevated lactic dehydrogenase, and elevated serum ferritin. The diagnosis was subsequently confirmed by a peripheral-blood smear revealing 60% of circulating blasts and bone marrow aspiration with 80% of blast infiltration. The latter was further classified through cytogenetic studies as an AML with deletion of chromosome 7q. This case report aims to highlight the need for clinicians to be aware of palatal necrosis as an initial manifestation of the disease and to emphasize the role of multidisciplinary collaboration between dental surgeons, oral and maxillofacial surgeons, and hematologists for early detection and treatment.