Gastrin levels have been reported to be often increased in patients with primary hyperparathyroidism (PHPT) considered to be caused by hypercalcemia. To determine the prevalence of increased basal gastrin and to investigate its causes, 52 consecutive patients with PHPT were studied prospectively, undergoing a clinical, biochemical, and gastric morphofunctional assessment before any parathyroid surgical procedure. This included evaluation of basal and secretin-stimulated gastrin, basal and pentagastrin-stimulated gastric acid secretion, upper gastrointestinal endoscopy, with histological evaluation for gastritis and Helicobacter pylori infection. Twenty of the 52 PHPT patients (38.5%) had increased fasting gastrin. Further investigation allowed us to clearly demonstrate the causes of hypergastrinemia in 16 of these 20 patients. In 7 of 20 (35%), hypergastrinemia was caused by gastric fundus atrophy; in 3 patients (15%), Zollinger-Ellison syndrome with Multiple Endocrine Neoplasia type I was diagnosed; whereas in another 20% of patients, mild hypergastrinemia was ascribed to Helicobacter pylori gastritis. Finally, in 2 patients, additional clinical history revealed an occasional use of the gastric antisecretory drug omeprazole a few days before the serum gastrin determination. This study shows that the hypercalcemic status per se is not sufficient to produce an increase in fasting gastrin levels. Furthermore, gastric fundus atrophy, and not gastrinoma, is the major cause of relevant (>160 pg/mL) hypergastrinemia.