Approximately 25% of B-cell acute lymphoblastic leukemia (B-ALL) cases are defined by hyperdiploidy, with RAS mutations occurring in 30% of hyperdiploid B-ALL patients.It is believed that hyperdiploidy is an in utero event with RAS mutations occurring postnatally, but clinical evidence of this is based on relatively few patients. We present a case of monozygotic, monochorionic twins who developed concordant hyperdiploid B-ALL with identical chromosomal gains but different RAS mutations, adding further evidence that hyperdiploidy is occurring prenatally, with RAS mutations developing postnatally. Environmental exposures were reviewed with the family without identification of a clear association.