The authors describe a clear cell chondrosarcoma of the larynx. The clear cell type is a rare variant of chondrosarcoma that only twice has been reported in this localization. The light-microscopic diagnosis of the actual case was confirmed by immunohistochemical results, in particular by positive staining for S-100 protein and collagen type II, and ultrastructural findings. Loss of heterozygosity analysis demonstrated allelic loss at 9p22 and 18q21, but neither in the region of the Rb gene on chromosome 13q nor at the p53 locus on chromosome 17p where allelic loss has already been reported in chondrosarcomas. Furthermore, our molecular genetic investigations revealed a methylation of the cell cycle control gene p16, which is localized on chromosome 9p. This characteristic has been recorded previously only in high-grade chondrosarcomas. Mutations in the exons of p16, alterations of the putative tumor suppressor gene MMAC1/PTEN on chromosome 10q, or an amplification of the cyclin D1 gene (CCND1) on 11q13, which were found to be changed in other studies of chondrosarcomas, could not be demonstrated here.