Unilateral condylar hyperplasia (UCH) of the temporomandibular joint is a progressive deformation of the mandibular condyle of unknown origin. UCH is characterized by excessive growth of the condylar head and neck, leading to an increase in size and volume. The aim of this study was to investigate the characteristics of the bone in patients with UCH using microcomputed tomography (micro-CT), histology, and Raman microspectroscopy. The mandibular condyles of six patients with UCH were analysed using micro-CT, histology, and Raman microspectrometry and imaging, and the results were compared with those obtained for a normal control subject. Three-dimensional micro-CT models revealed focal abnormalities of the bone microarchitecture, with foci of osteosclerosis. Histological sections showed that these foci included islands of calcified cartilage matrix with live chondrocytes. Raman analysis revealed that the cartilage matrix was more heavily calcified than the bone matrix and that the cartilage could be identified by the phenylalanine (PHE) band of its matrix, as well as by its glycosaminoglycan (GAG) content. The persistence of foci of live and active chondrocytes within the bone matrix is intriguing and appears to be pathognomonic of UCH. These new findings on UCH could help to determine its pathophysiology and thus prevent this disease, which can lead to major facial deformity.