In a multicenter prospective cohort-study we assessed the diagnostic yield of the Nordic guidelines for germline investigation in myeloid neoplasms (MN) and mapped the spectrum of inherited and somatic variants.Eighty-five patients (acute myeloid leukemia (AML): n=38; myelodysplastic syndromes (MDS): n=26; thrombocytopenia: n=14; other: n=7) fulfilling the Nordic criteria for germline investigation: (1) medical history (MH) or family history (FH) suggestive of a germline condition; (2), relevant findings from the somatic diagnostic work-up (CytoMol), were recruited. The genetic analysis included enhanced whole-exome sequencing (WES, n=69) or sequencing of specific variants of interest (n=16).Pathogenic or likely pathogenic (P/LP) germline variants were identified in 35% of patients (30/85). The diagnostic yield varied from 6% (1/16) in the FH group to 52% (17/33) in the CytoMol group. Germline DDX41 P/LP variants were the most frequent finding (13/30, 43% of all positive cases), almost exclusively found within the CytoMol group (12/13). Seven variants of unknown significance (VUS) were also detected (TERT n=2; DDX41, RTEL1, ETV6, PARN and SAMD9: n=1). Five patients carried a P/LP variant in genes associated with another hereditary cancer syndrome (BRCA1 n=3; PALB2 n=1; CHEK2; n=1). Survival analysis showed a trend for longer survival among patients with AML and confirmed or suspected germline predisposition that underwent allogeneic stem cells transplantation (allo-HSCT).The implementation of the Nordic guidelines in a prospective Swedish cohort, results in a high overall diagnostic yield (35%), proving the feasibility and utility of these or similar guidelines in a clinical setting.