The Dyggve-Melchior-Clausen syndrome is a rare inherited disorder in which a major feature, the skeletal dysplasia, is thought to result from a defect in endochondral ossification. To further characterize this disturbance, histochemical studies were performed on an iliac-crest biopsy specimen from a patient with disorder. The use of plastic embedding methods permitted previous observations, which were based on decalcified paraffin-embedded tissues, to be extended and a variety of new ones to be made. The resting cartilage matrix was very fibrous. In many areas it consisted of randomly oriented bundles of loosely woven fibers that stained as collagen. The chondrocytes in this region were excessively vacuolated and many contained cytoplasmic inclusions that stained non-specifically as protein. Cartilage canals were prominent in the resting cartilage. In many areas, clusters of degenerating chondrocytes and occasional vacuolar lesions replaced the columns of proliferating and maturing cells that normally occupy the growth-plate region. There was coarse and irregular calcification of these clusters at the chondro-osseous junction, and intracartilaginous ossification was also found. Clinical Relevance: These observations further define the histological criteria for the diagnosis of this disorder and provide new insights into its pathogenesis.