Angiosarcoma of bone is an exceedingly rare primary bone malignancy that can present as an aggressive osteolytic lesion. This subset can radiologically mimic non-vascular neoplasms and impose serious challenges in reaching the correct diagnosis. Meanwhile histological diagnosis can be extremely challenging too, as the pathological features often resemble that of aneurysmal bone cysts. We present an unusual case of a 22-year-old woman who presented with a rapidly growing humeral tumor of 8 months' duration. The case of intraosseous angiosarcoma presented as a diagnostic dilemma and the relevant radiological and pathologic findings were discussed. We describe the clinical, radiological and pathological features of this unique case, and review the literature concerning Angiosarcoma of bone. Our case highlights the diagnostic difficulties for such very rare tumours and clinico-pathological correlation is of paramount importance to differential diagnosis.