Introduction: Transient Abnormal Myelopoiesis (TAM) is a self-limiting myeloproliferative disorder seen in approximately 10% of neonates with Trisomy 21. It is characterised by marked leucocytosis with circulating blast cells and may be associated with anaemia, thrombocytopenia and organ dysfunction. Although TAM usually resolves spontaneously within three months, 20–30% of affected infants later develop acute myeloid leukaemia, particularly those with GATA1 mutations. Case presentation: A term neonate was delivered via normal vaginal delivery with a birth weight of 2.7 kg to non-consanguineous parents. The pregnancy was uncomplicated. On day one, the baby was admitted for grunting, and dysmorphic features suggestive of Trisomy 21 were observed. Initial full blood count revealed leucocytosis of 59,000/mm³, rising to 74,600/mm³ by day ten. There was no hepatosplenomegaly . Peripheral blood film showed numerous blast cells with occasional dysplastic neutrophils. The infant developed symptomatic anaemia requiring red cell transfusion. She was closely monitored for hyperviscosity and cardiac failure. By day 24, the white cell count decreased to 22,190/mm³. Paediatric oncology follow-up was arranged. At two months of age, the white cell count normalised to 7 ,300/mm³, with only occasional atypical cells on blood film. Continued haematological surveillance was advised. Conclusion: TAM is a transient but clinically significant condition in neonates with Trisomy 21. Although spontaneous resolution is common, careful monitoring is essential due to the risk of progression to acute myeloid leukaemia.