The hematological malignancies evolution exhibits significant differences with the solid tissue tumor development, especially in the initiation step. The loss of negative regulation theory of carcinogenesis was unambiguously demonstrated in the field of colorectal neoplasia, but up to date, several lines of inquiry failed to imply the dysregulation of suppressor genes as an etiologic event in the pathogenesis of leukemias and lymphomas. Considering the peculiarities of self-renewing hemopoietic cells, we propose in this communication a reconciliation of the loss of negative regulation theory with the blood malignancies development.