Giant cell tumors of the bone are local invasive diseases that are mainly composed of neoplastic monocytes and nonneoplastic multinucleated giant cells, mostly in the long bones of patients with mature bones. A specific H3F3A mutation is the key to its diagnosis. The present paper reports a case of giant cell tumor of the bone (GCTB) characterized by diffuse cholesterol crystals with few multinucleated giant cells. Imaging examination combined with immunohistochemical H3.3 G34W positivity was used to diagnose the patient with GCTB. Understanding the unique histological morphology of this patient will help doctors correctly diagnose giant cell tumors of bone and avoid misdiagnosis.