Bone metastases from differentiated thyroid cancer are generally resistant to radioiodine (RAI) therapy and are associated with poor prognosis. However, in a recent study from our group we noted a small subgroup of patients with RAI-avid bone metastases who had no structural correlate on imaging studies, and had no skeletal complications during follow-up. The purpose of this study was to better define the natural history and outcome of these patients. In a retrospective review of medical records at Memorial Sloan-Kettering Cancer Center, 288 patients were identified with bone metastases from thyroid cancer between 1960 and 2011. Out of this group, 14 patients who had a RAI-avid bone metastasis without structural correlate on CT or MRI were included in the study. After a median follow-up period of 5 years (range 2-14 years) all patients were alive, none had evidence of structural bone metastases, and none had experienced skeletal-related events. The final disease status was: no evidence of disease in 6 patients (43 %), stable biochemical persistence in 2 patients (14 %), stable structural disease in 5 patients (36 %), and one patient with slowly progressive disease. To conclude, RAI-avid bone metastases with no structural correlate on high-resolution imaging studies often resolve following RAI treatment, do not cause skeletal-related complications, and do not have a major prognostic significance. Recognition of this unique type of bone metastases is important as it is not associated with the same poor prognosis and resistance to RAI therapy that is associated with structurally identifiable bone metastases.