Introduction Ossification of ligamentum flavum (OLF) is a rare disorder. The present study aims at histopathological analysis of OLF with special emphasis on the alterations in the elastin fibers, collagen, matrix, cellularity, chodrocyte proliferation, and osteoid metaplasia. Materials and Methods The study involves histopathologic examination of surgically harvested ligamentum flavum (LF) specimens from 10 OLF, 5 with degenerative spinal stenosis and 5 normal LF as controls. The specimens were studied with hematoxylin and eosin, Verhoff van Gieson, toluidine blue, Masons trichrome, and Alcian blue. All specimens were analyzed qualitatively for (1) elastic fiber orientation, integrity, and loss, (2) collagen bundles,(3) fibrosis,(4) chondroid metaplasia,(5) chondrocyte proliferation, and (6) Osteoid metaplasia. The quantitative analysis was done using SCION image analysis software. Results All the 10 OLF specimens showed extensive loss of elastic fibers associated with cartilage matrix formation. There were many areas of irregularly oriented elastic fibers, areas of ossification and in between there was a transitional area of cartilage matrix with chondrocytes progressing toward ossification. Elastic fiber occupying ratio was 60.96, 40.25, and 22.66%; number of chondrocytes per mm2 was 37.56, 93.35, and 117.68; area of chondroid matrix (%) was 11.34, 32.37, and 73.56, respectively, and the area of osteoid matrix (%) was 0, 9.37, and 33.43 respectively for normal controls, degenerative group, and OLF group. The areas of cartilage matrix were more on the dorsal side compared with the dural side of LF. In contrast, cartilage matrix osteogenesis was more in dural than dorsal surface of LF. Conclusion In OLF, loss of elastic fibers was associated with proliferation of collagen fibers, fibrosis, chondrogenesis, and osteogenesis. The pathological process initiates in the dorsal surface with chondroid metaplasia gradually elevating the mature cartilage matrix toward the dural surface, where the initial ossification occurs. Disclosure of Interest None declared References Jolly SS. Fluoride balance studies in endemic fluorosis. Fluoride 1976;8:138–147 Jolly SS, Singh BM, Mathur OC, Malhotra KC. Epidemiological, clinical, and biochemical study of endemic dental and skeletal fluorosis in punjab. BMJ 1968;4(5628):427–429 Jolly SS, Singh ID, Prasad S, Sharma R, Singh BM, Mathur OC. An epidemiological study of endemic fluorosis in Punjab. Indian J Med Res 1969;57(7):1333–1346 Jolly SS, Prasad S, Sharma R, Rai B. Human fluoride intoxication in the Punjab. Fluoride 1971;4:64–79 Jolly SS, Prasad S, Sharma R, Chander R. Endemic fluorosis in Punjab-skeletal aspects. Fluoride 1973;6:4–18 Naidu MRC, Reddy DR, Reddy PK, Sastry Kolluri VR. [Fluorotic cervical spinal cord disease]. Rev Chir Orthop Repar Appar Mot 1989;75(4):228–231 Siddiqui AH. Fluorosis in Nalgonda District, Hyderabad-Deccan. BMJ 1955;2(4953):1408–1413