We observed three neoplasms with completely different histologies: malignant fibrous histiocytoma (MFH), atypical meningioma (AM), and glioblastoma (GB), developing in a patient with Li–Fraumeni syndrome. By using a combined molecular approach we performed molecular characterization of all three tumours. Data obtained showed an interesting molecular background of the AM and GB. AM showed TP53mutations and a 22q loss of heterozygosity (LOH). GB showed epidermal growth factor receptor (EGFR) amplification and TP53 mutations, whereas P16, PTEN, Rbwere intact in terms of LOH and/or multiplex PCR (polymerase chain reaction) analysis. Additionally, GB has a 1q LOH, which is an extremely rare alteration in glioblastomas. Identical 1q LOH was also observed in MFH.