This report describes the case of a 60-year-old woman with severe metabolic bone disease and fractures due to vitamin D deficiency and hyperparathyroidism. 25OHDH3 and 1,25(OH)2D3 serum levels were undetectable and increased immediately following 25OHD3 oral administration. Serum 1,25(OH)2D3 following vitamin D repletion reached values above the normal range, and remained elevated with strict dependence on the serum 25OHD3 levels. Parathyroid hormone and alkaline phosphatase decreased during treatment, without reaching normality during 1 year of observation. Bone biopsies before and after 8-month 25OHD3 treatment showed disappearance of the osteomalacic and hyperparathyroid lesions. During treatment an increase in serum and urine calcium and formation of renal stones were observed. The patient underwent neck exploration with the finding and removal of a lipoadenoma, a rare parathyroid tumor, followed by complete and permanent remission of the disease. In conclusion, this case is suggestive of the key role played by the long-term vitamin D status in the clinical expression of primary hyperparathyroidism.