BACKGROUND Primary hyperparathyroidism (PHPT) during pregnancy can be responsible for serious maternal and foetal complications and should be treated by elective low-risk, minimally invasive surgery. Preoperative assessment of hyperfunctioning parathyroid glands is classically based on high-resolution neck ultrasound (US) and 99mTc-sestamibi/123I scintigraphy. However, administration of any radiopharmaceutical during pregnancy must be limited and justified and US alone may be sufficient to localize an abnormal parathyroid gland. METHODS We report the case of a 4-month pregnant woman with severe primary hyperparathyroidism, in whom US failed to localize the abnormal parathyroid gland. 99mTc-sestamibi scintigraphy was performed in preference to 18-fluorocholine (FCH)-PET/CT on the basis of a multidisciplinary decision. As 99mTc-MIBI demonstrated an hyperfunctioning right inferior parathyroid, 123I was not administered. A large right paravertebral parathyroid adenoma was successfully removed, as confirmed by decreased postoperative serum parathyroid hormone and calcium levels. The eutrophic newborn infant was delivered at term, with normal serum calcium and TSH levels. CONCLUSIONS In pregnant women with primary hyperparathyroidism, US alone may be sufficient when it localizes the abnormal parathyroid gland, allowing elective low-risk minimally invasive surgery. Otherwise, a multidisciplinary approach is mandatory to select the radiopharmaceutical that can be safely used to identify the hyperfunctioning parathyroid gland with minimal risks for the foetus.