A 19-month-old female with Down syndrome presented with recurrent left cheek swelling and left eye involvement, initially diagnosed as fasciitis/myositis and periorbital cellulitis. Despite empiric antibiotics, symptoms persisted. A whole-body CT scan revealed prominent lymph nodes, and a biopsy of the buccal mass showed myeloid sarcoma. Bone marrow aspiration confirmed acute myeloid leukemia. Following chemotherapy, the patient’s symptoms resolved. This case underscores that acute leukemia may manifest as facial swelling or periorbital cellulitis, highlighting the importance of considering extramedullary myeloma in cases of persistent, unexplained soft tissue swelling that does not respond to standard treatments.