Most meningiomas carry mutations in the tumor suppressor neurofibromatosis gene 2 (NF2) on chromosome 22q, while NF2-wildtype meningiomas account for about a third of all meningiomas [4, 7]. In non-NF2-mutated cases, SMO, POLR2A, PIK3CA, AKT1, and KLF4 mutations, the latter both regularly with TRAF7 mutations, have been described [1,2,3, 5]. TRAF7, a E3 ubiquitin ligase which promotes degradation of p53 and p65 as well as a number of oncogenic protein targets, including NEMO, c-FLIP, and c-Myb, occurs in nearly one-fourth of all meningiomas (24% in Clark et al., 30% in Reuss et al.). However, some studies may have been enriched for specific subtypes. In almost half of the cases they co-occur with AKT1 (44% in Clark et al.) or KLF4 (36% in Clark et al.), respectively [3, 8]. The combination is intriguing: AKT1/TRAF7 mutations are associated with meningothelial histology and basal localization, while KLF4/TRAF7 mutations are highly specific for secretory meningioma without any predominant localization. Also, AKT1 and KLF4 have clear hotspots, with all mutations occurring at AKT1E17K or KLF4K409Q. In contrast, TRAF7 mutations can occur throughout the WD40 domain of the protein (Supplementary Fig. 4, online resource). The order of mutational acquisition, whether alterations in TRAF7 or in AKT1/KLF4 occurs first, remains elusive. The analyses here were initiated after diagnostic work-up of the tumors of a 47-year-old male patient with two independent meningiomas having identical somatic TRAF7 mutation N520S, but separate AKT1 (skull base, meningothelial) and KLF4 (convexity, secretory type) hotspot mutation (Fig. 1a). Of note, no TRAF7 mutation was detected in germline control DNA and surgical resection was performed at the same time. Although mere coincidence cannot be ruled out, this may be caused by a mosaicism for TRAF7 affecting arachnoidal cells, or a single ancestor of both tumors despite macroscopically separate location. Both the latter strongly suggest TRAF7 as the initiating mutation.