Giant cell tumor (GCT) of bone is a local, variably aggressive neoplasm with high local recurrence and occasional pulmonary metastases. Radiographically guided fine-needle aspiration (FNA) plays a large role in establishing a tissue diagnosis of lung metastases prior to therapeutic intervention. We present a patient with histologically proven pulmonary metastases from a femoral grade II GCT. These lesions were obliterated with combination HT-CT (hyperthermia and chemotherapy). The patient subsequently developed another pulmonary nodule at a site previously occupied by a GCT metastatic deposit. Radiographically guided FNA revealed that this new lesion was an adenocarcinoma, apparently of pulmonary origin. We suggest that this second neoplasm arose within a scar that developed after HT-CT ablation of one of the metastases. Additional intriguing features of this case are the effective HT-CT therapy of GCT metastatic to lung and the extended temporal course (some 16 yr from initial diagnosis to death).