The authors report two cases of secondary myelodysplasia and acute myeloid leukemia with t(3;21)(q26.3;q22) as the only cytogenetic abnormality in neoplastic bone marrow. This translocation was identified as a rare, recurring, non-random aberration in chronic myeloid leukemia less than five years ago and in secondary acute myeloid leukemia and myelodysplasia in 1990. The known and suspected cases in the literature are reviewed.