Mandibular swellings are most commonly odontogenic, inflammatory or primary neoplastic in origin, with hematologic malignancies representing a rare diagnostic consideration. We present a rare case of a 49-year-old male with a destructive mandibular lesion as the initial manifestation of a myeloid/lymphoid neoplasm with eosinophilia, characterised by a FIP1L1–PDGFRA gene rearrangement. The patient presented with preauricular swelling and inferior alveolar nerve hypoesthesia. Imaging revealed an osteolytic lesion in the mandibular ramus with soft tissue extension. Initial histopathology was inconclusive, demonstrating eosinophil-rich inflammation without obvious malignancy. Hematologic evaluation revealed marked eosinophilia and bone marrow abnormalities, and molecular testing confirmed a FIP1L1–PDGFRA fusion. Treatment with 100 mg daily imatinib led to rapid clinical resolution and complete radiologic disappearance of the mandibular lesion within three months. This case demonstrates that myeloid neoplasms with PDGFRA rearrangement can present with mandibular swelling and emphasises the clinical relevance of timely recognition, as these neoplasms are highly responsive to targeted tyrosine kinase inhibitor therapy.