The authors present a case of a 2-year-old girl with left ankle pain. On examination, there was tenderness but no sign of superficial swelling, erythema, or deformity. Imaging studies revealed a heterogeneous lytic lesion in the distal diaphysis of the left fibula, causing a pathologic fracture. The patient was treated with ankle splinting, analgesia, and referred to a pediatric orthopedic physician. Ultimately the diagnosis of acute lymphoblastic leukemia (ALL) was made. The authors present the significance of discerning skeletal abnormalities and orthopedic pain as the initial manifestation of leukemia.