In Brief Study Design. Retrospective case series and literature review. Objective. To describe our experience in diagnosis and management of patients with spine brown tumor (osteitis fibrosa cystica) as the initial manifestation of primary hyperparathyroidism and also to review the pertinent literature. Summary of Background Data. The spine can be involved through reparative processes such as giant cell reparative granuloma and brown tumor, which lead to formation of lesions that can simulate tumors on neuroimaging. Brown tumor, an uncommon focal giant cell lesion, is a nonneoplastic and reactive process due to bone resorption and localized osseous lesion caused by primary or secondary hyperparathyroidism. Methods. Among the cases of spine giant cell lesions treated surgically by the authors (2000–2013), there were 4 cases of spine brown tumor in patients with primary hyperparathyroidism. Clinical, radiological, histopathologic, and surgical data of these 4 cases were collected, and the patients were followed from 5 to 7 years after the surgical intervention. Results. There were 2 male and 2 female patients with age range of 16 to 52 years. The lesions were located in cervical (1 case), thoracic (1 case), and lumbar (2 cases) spine regions. Clinical presentations included neck and low back pain, radicular pain, paraparesis, and sphincter dysfunction. Surgical removal of the spine lesions was achieved in all cases. Spine fusion and instrumentation was done in 3 cases. Parathyroidectomy was performed in all 4 cases. Conclusion. Spine involvement with brown tumor in patients with primary hyperparathyroidism is rare and may be the first manifestation of hyperparathyroidism. Brown tumor should be differentiated from other giant cell lesions involving the spine. Long-term surgical outcome was satisfactory with no recurrence. Level of Evidence: 4 In this case series, we describe our experience with 4 patients who presented with spine brown tumor as the initial manifestation of primary hyperparathyroidism. All patients underwent surgical intervention to resect the spine lesions and were followed by parathyroidectomy. Long-term surgical outcome was satisfactory with no recurrence.