The case report presents a female patient with multifocal myeloid sarcoma in the soft tissues, skin, and lymph nodes in the presence of concomitant myelodysplastic syndrome in whom two series of inpatient induction chemotherapy (high-dose cyta-rabine and mitoxantrone, i.e. the HAM protocol) failed to induce complete remission and resolution of extramedullary lesions. Combined outpatient treatment with azacitidine (a hypomethylating agent) and venetoclax (a Bcl-2 inhibitor) has been shown to have a potential to overcome tumour chemoresistance.