In this case report we present a 44-year-old woman with a 2-weekhistory of vaginal bleeding. Gynaecological examination revealed the presence of a polypoid neoformation in the endometrial cavity with a maximum diameter of 4 cm. Histological analysis showed a classic leiomyoma infiltrated by a second monomorphic, highly undifferentiated neoplasia. Immunohistochemical analysis revealed a negative reaction for cytokeratin, CD10, inhibin, CD99, CD20, CD3, TdT and CD34, and positivity for CD45, MPO, CD68 and CD117. A diagnosis of myeloid sarcoma in myometrial leiomyoma was made. The following days the patient showed the onset of an acute myeloid leukaemia M5a. Forty days after diagnosis the patient died for complications related to immunodeficiency caused by therapy. Especially when a common antibody panel reveals negativity for epithelial, mesenchymal and lymphoid markers, this case underlines the importance of considering myeloid sarcoma in differential diagnosis of undifferentiated tumours arising in an extramedullary site in order to avoid errors and permit optimal therapeutic management.