Fifty-six patients with a major constitutional chromosome anomaly and a malignant hematologic disorder in whom the chromosomes of the malignant cells were analyzed by banding techniques are reported from a cooperative and retrospective study. The patients included 25 with trisomy 21, nine with a sex chromosome anomaly, and 22 with a structural rearrangement. For Down's syndrome patients, the morphologic and cytogenetic aspects of acute leukemia were studied because it has been postulated that there could be a specific pattern of acute leukemia in Down's syndrome patients. For other chromosome rearrangements detailed karyotypic changes are reported, but the question of whether these patients are at greater risk of hematologic malignancy remains unanswered.