Li-Fraumeni syndrome greatly increases the risk of developing several types of cancer and is usually caused by TP53 germline mutations. Predictive testing of at-risk family members is only offered after a complex genetic counseling process. Recently the clinical implementation of array comparative genomic hybridization (CGH) has revolutionized the diagnosis of patients with syndromic or nonsyndromic mental retardation and has evolved to a routinely performed high-resolution whole-genome scan. When using array-CGH to identify the cause for mental retardation in a seven-year-old child we found a submicroscopic de novo deletion of chromosome 17p13.1, which includes several genes likely to be causative for her phenotype, and also of TP53. Thus, array-CGH resulted in an unintended predictive diagnosis of an increased tumor susceptibility as observed in Li-Fraumeni syndrome.