Results of cytogenetic studies of 100 cases of suspected or proven leukemia show that significant spontaneous division in 24 hr. peripheral blood cultures is indicative of an abnormal state. If viremia can be ruled out clinically, and the spontaneous division is persistent, a leukemic process is suggested even before the development of overt leukemia. Application of the described criteria has been accurate in distinguishing betweeen leukemic and nonleukemic states, even in “preleukemic” and aleukemic conditions. The technic may also predict those cases of myeloproliferative disorders in which malignant transformation will occur. The results show that the presence of structural chromosomal abnormalities in the marrow (except for the Philadelphia chromosome) may not be diagnostic of leukemia unless the mitotic criteria are met. Our preliminary studies show that the combination of mitotic determination and karyotypic analysis will give an accuracy of 97% in the diagnosis of leukemia, while mitotic studies alone are 85% accurate. Therefore, it would appear that peripheral blood cultures should be used in addition to marrow in cytogenetic studies for diagnosis of leukemia, employing the criteria developed in this laboratory.