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Acute leukemias are rare disease in the neonatal period. They occur preferentially in newborns with trisomy 21. They often manifest as hepatosplenomegaly, extra-hematopoietic involvement and hyperleukocytosis. Blueberry Muffin Baby syndrome is observed in the neonatal period. Neonatal acute myeloïd leukemia (AML) is more common than acute lymphoid leukemia (ALL). Despite treatment, neonatal acute leukemias have a poor prognosis with a low percentage of overall survival. We report a case of neonatal AML on a ground of trisomy 21 revealed by a Blueberry Muffin Baby syndrome.