The lineage affinity of 61 cases of acute unclassified leukemias (AUL) was reevaluated by ultrastructural analysis of peroxidase expression (POEM) in combination with immunophenotyping. In 24 cases a significant proportion of the blasts displayed ultrastructural myeloperoxidase (UMPO) and in another 3 cases platelet peroxidase (UPPO) suggesting the allocation of these leukemias to the myeloid or megakaryoblastic lineage. No significant correlation between myeloid surface marker expression and POEM positivity could be detected, while the presence of the CD 19 or CD 24 antigen significantly correlated with POEM negativity. The detection of lymphoid markers on POEM+ blasts indicates, that these leukemias might be derived from bipotential progenitors, which have retained their lymphoid antigens during myeloid differentiation. In one case a bilineage leukemia with a POEM+/CD 19- and a POEM-/CD 19+ population could be identified by immunoelectron microscopical studies (IEM). The remaining 34 AUL cases were POEM negative. Combined data suggest that these cases probably derive from early lymphoid progenitors. Taken together, AUL are heterogenous in presentation and in their cellular origin including a major portion of cases with an unequivocal myeloid differentiation detectable by ultrastructural analysis of myeloperoxidase expression.