Giant cell tumor of bone is an aggressive lesion, although benign. Foot and ankle involvement is rare. Herein, we presented a case of a 26-year-old woman complaining of increasing pain and swelling of the left ankle followed by limitation of joint motion. Imaging was consistent with the diagnosis of giant cell tumor of bone, which was confirmed by open biopsy. The lesion was treated with segmental en-bloc resection and ankle arthrodesis with good functional outcome. We also discuss clinical, radiological, and therapeutic characteristics of this pathology with the light of the literature.