Hematopoietic tumors in both humans and mice frequently up-regulate expression of the c-myb gene, but it is unclear whether this is a cause or a consequence of the leukemic state. Recent results placing superactivation of the c-Myb protein at the bottom of a kinase-activated signal transduction pathway indicate that it may be a downstream effector of transformation induced by other oncogenes. The relationship between c-Myb and the serine-threonine kinase pim-1, its immediate activator, is discussed, together with the possibility that c-Myb, like pim-1, may be able to synergize with c-Myc to induce tumors.