We describe a case of a 38-year old male with inv(16)(p13q22) positive acute myeloid leukaemia (AML) with eosinophilia, relapsing after a molecular remission of almost three years. Remarkably, the leukaemia at relapse was identified as a precursor-B-cell acute lymphoblastic leukaemia (B-ALL) by cytology and immunophenotyping, but was inv(16)(p13q22) positive as revealed by interphase FISH, FICTION analysis, and real-time quantitative PCR. Analysis of immunoglobulin and T-cell receptor genes showed a bi-allelic DH2-JH rearrangement at relapse, but not at diagnosis. These findings indicate a myeloid to lymphoid lineage switch from an inv(16)(p13q22) positive leukaemia and show that IGH gene rearrangements can occur in the presence of CBFB-MYH11 fusion transcripts.