ABSTRACT Background: A variety of factors influence the prognosis of acute myeloid leukemia (AML), and leukemic stem cells (LSCs) are one key prognostic factor that predicts poor prognosis over the course of the disease. G protein–coupled receptor 56 (GPR56) was presented as a new human LSC marker in AML patients. The engraftment potential of GPR56+ cells selected from AML specimens helps the spread of leukemia in mice, which supports the concept of using it as an LSC marker.  Aim of the Work: The objective of this study was to use flow cytometry to investigate GPR56 expression in newly diagnosed AML patients. The results of GPR56 expression were linked to the patients' clinical outcomes. Subjects and methods: Forty AML patients and 20 healthy control subjects were evaluated for GPR56 expression on myeloblasts. At the end of induction treatment, bone marrow aspirates were obtained for assessment of morphological remission and minimal residual disease analysis. Results: GPR56 levels were significantly higher in control subjects than in AML patients. AML patients who failed to achieve complete remission were more likely to show high levels of GPR56. However, a relationship to long term follow up data was not evident in our results. Conclusion: Despite the lack of a direct prognostic influence of GPR56 on patient outcome or a relationship to prognostic cytogenetic subgroups, the association of GPR56 with a poor prognostic marker, early response to therapy, can be regarded an evidence of the speculated bad prognostic impact of GPR56.