Patients with Li-Fraumeni syndrome (LFS) have a germ-line mutation of p53 (TP53) and are predisposed to develop a variety of malignancies at an early age. In this report, we describe an 18-year-old woman with LFS who developed an atypical fibroxanthoma (AFX) on her left arm. This tumor was based in the dermis, sparsely cellular and had ill-defined borders. It was composed predominantly of medium-sized spindled-shaped cells, but many large cells with pleomorphic nuclei were also present. Immunohistochemical stains showed that the tumor cells lacked expression of keratin, S-100 protein, desmin and CD34. Array-based comparative genomic hybridization (aCGH) revealed marked genomic instability with multiple whole chromosome losses, including chromosomes 8, 10, 13 and 22, as well as a partial loss of 17p. This represents one of a few reports of a cutaneous tumor in a patient with LFS and a rare example of an AFX occurring at a young age.