We describe a case of cutaneous T-cell lymphoma occurring in a 21-year-old male with Wolf-Hirschhorn syndrome (WHS) due to a chromosome 4p16.3 deletion. This is the first documented case report of malignancy occurring in an adult with WHS. We also review the literature regarding patients with WHS and the joint occurrence of malignancy and discuss genetic changes involving chromosome 4 which may have contributed to the genesis of our patient's lymphoma. (C) 2003 Wiley-Liss, Inc.