The study describes 10 individuals from 6 families with genetically confirmed RUNX1-familial platelet disorder with associated myeloid malignancy (RUNX1-FPDMM). Patients' platelet counts ranged between 40 and 208 G/L, with all subjects having impaired platelet aggregation to stimuli such as collagen, ADP and epinephrine. In three of the eight tested, a significant disorder of the secretion of platelet granules was detected. Genetic variants of RUNX1 included whole-gene deletions, intragenic deletions, missense variants, and mosaic loss of the gene, suggesting a diverse genetic cause of the disease. One patient developed acute myeloid leukemia and another developed TMM-RUNX1 associated with thrombocytopenia and lymphoma. Diagnostics using an NGS panel, Sanger sequencing, karyotyping and FISH were key to identifying these variants. The increased risk of hematological malignancies and bleeding resulting from qualitative disorders of platelet function emphasizes the need for genetic testing and caution in the treatment of patients, especially before invasive procedures.