Herein, we describe a unique case of anaplastic de novo astroblastoma-sarcoma, in essence a variant of gliosarcoma, occurring in a 50-year-old female with documented NF1. Genetic study (fluorescence in situ hybridization) demonstrated no chromosomal losses or gains. Testing for abnormalities of chromosomes 7, 9, 10, 12, 17, 19 and 20, including the EGFR, p16, PTEN, MDM2 and NF1 gene regions, we found the tumor to exhibit a deletion of PTEN, monosomy 17 and gains of chromosomes 19 and 20q.