Parathyroid lipoadenoma is an unusual cause of primary hyperparathyroidism. Only a few earlier reports have documented parathyroid imaging in diagnostic studies of parathyroid lipoadenoma. Our case was a 27-year-old man, who was originally diagnosed with primary hyperparathyroidism. He underwent a Tc-99m sestamibi dual-phase parathyroid imaging study, which revealed a right-inferior parathyroid hyperfunctional lesion. The first operation removed a lesion of 1.5 cm in diameter in the area, and parathyroid lipoadenoma was diagnosed by pathology. However, hypercalcemia persisted. One week later, a Tc-99m sestamibi whole-body scan and another dual-phase imagining were performed, which demonstrated a residual lesion in the inferior part of the right thyroid region, while no ectopic lesion was found. A second surgery was performed and pathological diagnosis was confirmed as parathyroid lipoadenoma again. Our case demonstrated that although hyperfunctional parathyroid lipoadenoma is rare, Tc-99m sestamibi parathyroid imaging is reliable in locating the lesion for surgical purposes. And Tc-99m sestamibi imaging is useful in reoperative and persistent hyperparathyroidism situations as well.