Lipoadenoma is the accepted diagnosis of a single enlarged parathyroid gland that contains large quantities of mature fat cells and focal myxoid stroma, all widely separating small parenchymal cell nests in patients with hyperparathyroidism. Here we are reporting, for the first time, on five cases of hyperparathyroidism in which all four parathyroid glands are enlarged and each gland is noted to have an admixture of fat and parenchymal cells. We will introduce the descriptive diagnosis of lipohyperplasia to name this condition and keep it in perspective with other forms of parathyroid disease. All five patients were women between the ages of 36 and 62 years who underwent neck exploration, at which time four enlarged light-tan parathyroid glands were observed. Three and one half gland resections were performed, and all patients returned to a normocalcemic state except one who had borderline serum hypercalcemia after operation. Most of the resected parathyroid glands weighed in the range of 100 to 200 mg. The largest measured gland weighed 820 mg. Parathyroid histology showed an admixture of mature fat cells with parathyroid parenchymal cells often in a 1:1 ratio. One patient who had renal failure exhibited a lower ratio of fat cells. Two patients had chronic lymphocytic thyroiditis that was severe enough to require synthetic thyroid hormone therapy. Two patients had a history of urinary tract infections. Three patients had hypertensive cardiovascular disease, and several patients had arteriosclerotic cardiovascular disease. One patient had diabetes mellitus, one had a history of pituitary adenoma, and one had polydipsia. All of these patients were first seen with parathyroid glands measuring an average of five times normal size, yet they showed the usual 50% fat/50% parenchyma pattern of normal mature parathyroid glands. This means that the enlarged glands contain a 500% increase in parathyroid tissue, justifying the diagnostic term "lipohyperplasia." This easily represents enough parathyroid tissue to generate excessive parathyroid hormone production. At this time, there is no explanation of the pathogenesis of lipohyperplasia or how it varies from other previously described forms of parathyroid hyperplasia.