Congenital leukemia is a rare disease accounting for about 1% of all leukemias in childhood. While cases associated with Down's syndrome not infrequently show a spontaneous regression, such an event is very rare in non-Down cases and exceptional in those (among the latter) which present clonal cytogenetic alterations in the neoplastic cells. We present the case of a patient with congenital leukemia and an abnormal karyotype (limited to the neoplastic clone), in which an apparently spontaneous and prolonged remission occurred after a relapse.