Eighteen cases of pediatric acute multi-phenotypic leukemia from 24 French centers investigated during 5 years are reported. The multi-phenotypic character of these cases was shown by the paradoxical presence of 2 or 3 associated membrane antigens which are normally lineage restricted. The following bi-phenotypic combinations were found: B/T lymphoid (n = 6), B/myeloid (n = 7) or T/myeloid (n = 2). Three cases of tri-phenotypic association were also observed [B/T/myeloid (n = 2), B/myeloid/megakaryoblastic (n = 1)]. Our findings suggest that combinations with a myeloid composant and the presence of cALLA (common acute lymphoid leukemia antigen) on less than 45% of cells seem to be related to a shorter survival.