Primary hyperparathyroidism (PHPT) is one of the most common endocrine diseases. Its clinical presentation has dramatically changed in the last 40 years, and now the disease typically affects elderly women and is characterized by mild hypercalcemia and few traditional classic (bone and kidney) manifestations. The change in clinical presentation was largely caused by development of automated serum calcium measurement in the early 1970s that made possible the introduction of serum calcium determination in the routine biochemical screening and the identification of a large number of "asymptomatic" patients. This led also to a 5-fold increase in the apparent incidence of PHPT for the identification of patients who were never diagnosed before (catch-up effect). From the most recent and accurate study, a 21/1000 PHPT prevalence was found in women aged 55-75 years, which is equivalent to 3/1000 prevalence in the general population. Epidemiological studies performed in Rochester, Minnesota, have shown an apparent decline in the annual incidence from 75 to approximately 20/100,000 in the last decade. Most of this apparent decline in the incidence of PHPT is explained by the decline of the "catch-up effect," although a number of factors that might result in changes in PHPT incidence have been identified. Vitamin D deficiency is particularly common in people living in Southern European countries, and this may contribute to underestimating the prevalence of PHPT, because total serum calcium may be normal in these patients. On the other hand vitamin D deficiency may be associated with more severe clinical expression of the disease, which may make clinically manifest otherwise mild asymptomatic cases. Irradiation of the neck and upper chest for benign diseases is a well-known risk factor for the development of PHPT, and a history of irradiation can be obtained in as many as 15-25% of PHPT patients. Because this therapeutic procedure is no longer used, the number of radiation-associated cases of PHPT is expected to progressively decline in the future. Restriction of healthcare financing may also contribute to the apparent decrease in the incidence of PHPT because calcium measurement is now performed only in patients who have a suspected abnormality in calcium homeostasis is. On the other hand, the screening for osteoporosis, which often includes serum calcium determination, is increasingly carried out in women around the sixth decade of life, when the incidence of PHPT is by far more frequent. In conclusion, the introduction of serum calcium screening in the early 1970s exerted an impressive effect on the epidemiology of PHPT, with an apparent incidence initially rising and then falling by the 1990s secondary to the diminution of the "catch-up effect." Other environmental, nutritional, or iatrogenic factors might influence the incidence of the disease, but the overall effect is unlikely to be relevant.