The malignant transformation of conventional giant cell tumor of bone (GCTOB) is rare and usually occurs with irradiation. Here we report two neglected cases of conventional GCTOB with spontaneous malignant transformation at 11 and 16 years after initial diagnosis. In the former case, the patient refused to receive any treatment following the incisional biopsy, and in the latter, the first recurrence that occurred 5 years after initial treatment, was neglected. Although rare, the occurrence of sarcomatous changes in these cases indicates that secondary malignant transformation may be part of the natural course of this tumor. In addition, in both cases, immunohistochemistry showed diffuse and strong p53 expression in the malignant tumor but not in the primary lesion. It suggests that p53 overexpression may play a key role in the malignant transformation of GCTOB and that investigating for p53 expression in recurred lesions may help in predicting cases of giant cell tumor, prone to malignant transformation.