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The 85% of cases of primary hyperparathyroidism (PHPT) are due to parathyroid adenomas (PA) and less than 1% to parathyroid carcinomas (PC). The PA usually measure <2 cm, weigh <1 g and generate a mild PHPT, whereas the PC usually exceeds these dimensions and are associated with a severe PHPT. However, giant PA (GPA), which is defined as those larger than 3 g, has been documented. Those may be associated with very high levels of PTH and calcium. In these cases, their differentiation before and after surgery with PC is very difficult. We present a case of severe PHPT associated with a large parathyroid lesion, and we discuss the differential aspects between the GPA and PC.Learning points:In parathyroid lesions larger than 2 cm, the differential diagnosis between GPA and PC should be considered.Pre and postsurgical differentiation between GPA and PC is difficult; however, there are clinical, analytical and radiographic characteristics that may be useful.The depth/width ratio larger or smaller than 1 seems to be the most discriminatory ultrasound parameter for the differential diagnosis.Loss of staining for parafibromin has a specificity of 99% for the diagnosis of PC.The simultaneous presence of several histological characteristics, according to the classification of Schantz and Castleman, is frequent in PC and rare in GPA.