The parathyroid hormone-related peptide (PTHrP) has been shown to be the major pathogenic factor to humoral hypercalcemia of malignancy (HHM). The presence of PTHrP in many normal tissues and in normal or abnormal parathyroids has been described in literature and its role has been investigated. PTHrP release from parathyroid cells into the extracellular space has been demonstrated to depend on the extracellular calcium concentration. The hormone binds to PTH type 1 Receptor (PTH1R) with a high affinity, as well as parathyroid hormone (PTH). These hormones' amino-terminal (1-34) peptide fragments are considered sufficient to achieve efficient receptor activation and action on mineral ion homeostasis. Generally, diagnosis of primary hyperparathyroidism (PHPT) is based on hypercalcaemia and elevated levels of PTH. The advent of intact-PTH immunoradiometric assay allowed us to distinguish PHPT from non-parathyroid-dependent hypercalcaemia, but the presentation of normal PTH level and hypercalcaemia due to a parathyroid adenoma is possible. The aim of the study is to identify the relationship between the production of PTHrP without malignancy and the diagnosis of PHPT by a systematic review.