The scapholunate interosseous ligament (SLIL) plays a fundamental role in stabilizing the wrist bones, and its disruption is a frequent cause of wrist arthrosis and disfunction. Traditionally, this structure is considered to be a variety of fibrocartilaginous tissue and consists of three regions: dorsal, membranous and palmar. Despite its functional relevance, the exact composition of the human SLIL is not well understood. In the present work, we have analyzed the human SLIL and control tissues from the human hand using an array of histological, histochemical and immunohistochemical methods to characterize each region of this structure. Results reveal that the SLIL is heterogeneous, and each region can be subdivided in two zones that are histologically different to the other zones. Analysis of collagen and elastic fibers, and several proteoglycans, glycoproteins and glycosaminoglycans confirmed that the different regions can be subdivided in two zones that have their own structure and composition. In general, all parts of the SLIL resemble the histological structure of the control articular cartilage, especially the first part of the membranous region (zone M1). Cells showing a chondrocyte‐like phenotype as determined by S100 were more abundant in M1, whereas the zone containing more CD73‐positive stem cells was D2. These results confirm the heterogeneity of the human SLIL and could contribute to explain why certain zones of this structure are more prone to structural damage and why other zones have specific regeneration potential.Research HighlightsApplication of an array of histological analysis methods allowed us to demonstrate that the human scapholunate ligament is heterogeneous and consists of at least six different regions sharing similarities with the human cartilage, ligament and other anatomical structures.