A 66-year-old woman with acute monoblastic leukemia with t(11;22)(q23;q11), which was subsequently transformed into myeloblastic leukemia is reported. Such karyotype abnormality has not been reported in acute monoblastic leukemia. Cytogenetic analysis revealed 47,XX,+8,t(11;22)(q23;q11) in 19 out of 20 metaphases and 46,XX,del(7)(q22-q36),t(11;22)(q23;q11) in the remaining metaphase. Variant Ph1 was ruled out due to the absence of chimeric bcr-alb mRNAs. In remission cytogenetic findings showed normal karyotype. After 4 months, the patient relapsed with 20% myeloblasts replacing monoblasts in bone marrow. Cytogenetic analysis revealed 46,XX,del(7)(q22-q36),t(11;22)(q23;q11) in all metaphases. A possible explanation for this lineage switch may be the involvement of myelomonocytic progenitor cells.