Objective: Congenital Leukemia (CL) is an extremely rare malignant condition with an incidence rate of fewer than five cases per 1 million live births in neonate mostly non-lymphoblastic leukemia in contrast to predominance of ALL found in later childhood. CL may be associated with syndromic conditions including Down’s syndrome.

Case presentation: A 29-day-old male neonate will be presented with lethargy, poor feeding and mild hepatosplenomegaly, manifestations suggestive of sepsis and negative sepsis work-up. Physical examination showed that the patient was febrile and pale, with facial syndromic appearance suggestive for Down’s syndrome. His peripheral blood smear showed severe leukocytosis, thrombocytopenia and atypical cells. Bone marrow examination revealed increased myeloblasts but no nucleated-RBC; confirmatory investigations finalized diagnosis of congenital leukemia. Karyotyping indicated chromosome 21-trisomy pattern.

Conclusions: Leukemia needs to be approached in such conditions with clinical features of sepsis and leukocytosis besides an oriented look for co-incident abnormalities.