Secondary and tertiary hyperparathyroidism (HPT) are common complications in patients with end-stage renal disease (ESRD) and may result in renal osteodystrophy. While [18F]-FDG PET/CT is primarily used to evaluate malignancy, it may occasionally reveal metabolic or endocrine abnormalities. A 45-year-old male with ESRD on hemodialysis presented with generalized bone pain and radiologic suspicion of malignancy. [18F]-FDG PET/CT demonstrated diffusely increased skeletal uptake and multifocal lytic bone lesions, consistent with metabolic bone disease secondary to renal osteodystrophy. Incidental findings of soft tissue nodules in both tracheoesophageal grooves suggested parathyroid pathology. Subsequent [99mTc]-Tc-sestamibi SPECT/CT confirmed parathyroid adenomas/ hyperplasia. Laboratory tests revealed elevated calcium (10.8 mg/dL), phosphorus (7.2 mg/dL), and markedly increased parathyroid hormone (3120 pg/mL) levels.This case highlights that diffuse skeletal [18F]-FDG uptake in ESRD may mimic malignancy but actually represent metabolic bone disease due to secondary or tertiary HPT. The [18F]-FDG PET/CT findings of parathyroid lesions were incidental, while [99mTc]-Tc-sestamibi SPECT/CT accurately localized the hyperfunctioning glands. FDG PET/CT can incidentally demonstrate metabolic bone disease and parathyroid-[18F] abnormalities in ESRD, but [99mTc]-Tc-sestamibi SPECT/CT remains the preferred modality for parathyroid localization. Awareness of this potential finding may prevent misinterpretation and guide appropriate management.