Histologically proven bone islands exhibiting increased FDG uptake have been rarely reported before. We present a case with active giant bone island in the left humerus showing increased FDG uptake with SUVmax of 3.8. The diagnosis was confirmed by open biopsy and follow-up. Increased osteoblastic activity, proliferating and active fibroblasts, and increased blood flow may contribute to the increased FDG uptake of this giant bone island. This case indicates bone island should be included in the differential diagnosis of abnormal FDG uptake in focal sclerotic bone lesions, especially in patients with known malignancy.