Transient myeloproliferative disorder (TMD) typically presents with pancytopenia, hepatosplenomegaly, and immature circulating white blood cells, and affects approximately 10 % of neonates with Down syndrome. The authors report a neonate with Down syndrome who developed acute widespread pustular eruptions as a sign of TMD. The white blood cell counts on the first day of life were markedly elevated, with blasts seen on examination of the peripheral blood smear. And the patient was noted to have a few erythematous papules and pustules especially on the face. On the following days pathergy positive crusted papules and pustules were increased and spread to trunk and extremities. Skin biopsy specimens showed pustular dermatitis, with subcorneal vesiculopustules and perivascular inflammation in superficial dermis. These lesions improved parallel with the hematologic improvement within two weeks. The authors aim to alert clinicians about this uncommon cause of vesiculopustular eruption with the present illustrative case and review the literature.