Primary hyperparathyroidism (PHPT) may occur sporadically or within MEN syndromes. It is classically thought that PHPT in MEN occurs at earlier ages than sporadic PHPT without significant differences in clinical and biochemical presentation. The aim of the study was to compare clinical and biochemical parameters between sporadic PHPT and MEN1 patients. The study included 41 genetically diagnosed MEN1 patients (14M, 27F) and 88 sporadic PHPT patients (24M, 64F) matched for age at diagnosis. All PHPT patients were studied for calcium metabolism parameters and renal and bone complications and evaluated for familial history and the presence of signs or symptoms possibly related to MEN1. Young (<50 ys) MEN1 patients showed significantly lower serum PTH (71.23±50.89 vs 224.42±220.20 mg/dl, mean±SD, P=0.019), total (11.05±0.56 vs 12.02±1.22 mg/dl, P=0.015) and ionized calcium levels (1.48±0.07 vs 1.62±0.19 mmol/l, P=0.021) compared with age-matched sporadic PHPT patients, while such differences were not detected in old (5170 ys) MEN1 vs sporadic PHPT patients. Despite the low PTH and calcium levels in MEN1, the prevalence of nephrolithiasis and osteoporosis was similar in the two PHPT forms. A female to male ratio of 1:1 was observed both in MEN1, as expected, and young sporadic PHPT patients. Moreover, young sporadic PHPT patients showed significantly higher serum calcium levels than the old patients (12.0±1.2 vs 11.2±0.9 mg/dl, P=0.008), in contrast to the pattern observed in MEN1. Our data suggested that milder hypercalcemia and PTH levels within the normal range were not uncommon in young MEN1 with respect to young sporadic PHPT patients, though both groups of patients did not differ for renal and bone complications. In conclusion, young symptomatic hyperparathyroid patients with slightly elevated serum calcium and PTH levels should be carefully screened for MEN1 diagnosis.