Mack, M

ABSTRACT Approximately 10% of patients with Ewing sarcoma (EwS) have pathogenic germline variants. Here, we report two cases: first, a novel germline pathogenic variant in partner and localizer of BRCA2 ( PALB2) in a patient with a late EwS relapse. Its impact on homologous recombination is demonstrated, and breast cancer risk is discussed. Second, we report a pathogenic germline variant in RAD50 in a patient with a rare prostate primary EwS and later concurrent relapsed EwS and therapy‐related acute myeloid leukemia (tAML) with two rare KMT2A translocations. Understanding rare pathogenic germline variants and the impact on cancer behavior, response to treatment and treatment‐associated toxicities is important for patients.