The p53 homologue p73 is expressed in at least six different isoforms (alpha, beta, gamma, delta, epsilon, and zeta), but unlike p53 it has rarely been found mutated in human cancers. However, altered expression of this gene has been reported in cancer cells. In order to understand if p73 is involved in normal and malignant development of myeloid cells, we investigated the expression pattern of the different p73 isoforms in progenitor and mature normal myeloid cells as well as in cells derived from acute and chronic myeloid leukemias. The results show that expression of p73 is markedly enhanced during differentiation of myeloid leukemic cells and that leukemic blasts from patients show an increased expression of the shorter p73 isoforms (gamma, delta, epsilon, zeta). In particular the epsilon isoform is only expressed in leukemic cells and completely absent in mature myeloid cells. Altogether our data suggest that p73 is involved in myeloid differentiation and its altered expression is involved in leukemic degeneration.