Molecular and cytogenetic studies performed in 305 adult acute lymphoblastic leukaemia (ALL) patients enrolled in the gimema (Gruppo Italiano Malattie EMatologiche dell'Adulto) multicentric protocols identified an E2A–PBX1 fusion and/or t(1;19) in 10 patients (3·3%). All had common ALL, were mostly CyIg⁺ and were CD34/CD13/CD33^–. Nine patients achieved a complete remission (CR); five patients showed a haematological relapse after 7 months (median). Four patients are alive in first CR with a median follow‐up of 29 months; three patients are molecularly negative. This abnormality is frequently associated with early treatment failure. E2A–PBX1⁺ adult ALL should be considered for intensified treatment strategies and monitoring of minimal residual disease.