Immunophenotyping disclosed CD10 negativity in 70 of 2408 cases of B-lineage acute lymphoblastic leukemia (ALL), although other criteria followed classification of pre-B ALL (eg, cytoplasmic immunoglobulin positivity). These blasts showed high myeloid antigen expression (60% CD65 positivity) and reacted with antibody 7.1 in 95% of the cases. MLL-AF4 fusion transcripts or an 11q23/MLL rearrangement or both were evident in 46 of 56 samples (82%). Although 83% of the patients achieved complete remission, the remission duration remained remarkably low: 141 days for MLL rearrangement-positive and 245 days for MLL rearrangement-negative CD10(-) pre-B ALL. Thus, the overall survival probability 3 years after diagnosis was 0.34 +/- 0.20 SE in MLL-rearrangement-negative versus 0.12 +/- 0.06 SE in MLL rearrangement-positive CD10- pre-B ALL. Our data identify CD10- cytoplasmic immunoglobulin-positive pre-B ALL as a rare (2.2%) but distinct immuno-subtype of adult ALL that is characterized by a high MLL rearrangement rate and a worse outcome.