Abstract Revised diagnostic criteria for myeloid neoplasms (MN) issued by the International Consensus Classification (ICC) and the World Health Organization (WHO) recommended major change pertaining to TP53-mutated (TP53 mut) MN. However, these assertions have not been specifically examined in therapy-related myeloid neoplasm (t-MN), a subset enriched with TP53 mut. We analyzed 488 t-MN patients for TP53 mut. At least one TP53 mut with variant allele frequency (VAF) ≥ 2% with or without loss of TP53 locus was noted in 182 (37.3%) patients and 88.2% of TP53 mut t-MN had a VAF ≥10%. TP53 mut t-MN with VAF ≥ 10% had a distinct clinical and biological profile compared to both TP53 mut VAF 10% blasts had inferior survival compared to