A 49-year-old Japanese woman was diagnosed on March 1996 as having thyroid cancer with lung metastasis. Following a total thyroidectomy, she was treated with a total dose of 350 mCi iodine-131 (131I) for metastatic thyroid cancer. Four years later she returned to our hospital under the chief complaint of subcutaneous bleeding. Hematological examinations revealed marked leukocytosis associated with anemia and thrombocytopenia. A bone marrow aspiration showed a hypercellular marrow consisting of 90% blasts negatively stained by myeloperoxidase. Immunophenotyping of the blasts indicated they were CD19, 34, HLA-DR positive but CD3, 10, 13 negative. She was given the diagnosis of pro-B acute lymphoblastic leukemia (pro-B ALL). Cytogenetic analysis showed a chromosomal aberration t(4; 11)(q21; q23) and MLL-AF4 chimeric gene mRNA was detected by RT-PCR analysis. She had never been exposed to any kind of chemoradiotherapy other than 131I therapy and her leukemia showed a t(4; 11) chromosomal aberration and no expression of CD10 on the blasts, which are the characteristics frequently found in therapy-related pro-B ALL patients, suggesting a relationship between the development of pro-B ALL with t(4; 11) and 131I therapy. Although leukemia has been recognized as a late uncommon complication after 131I therapy for thyroid cancer, to the best of our knowledge this is the first patient who developed ALL with t(4 ;11) after 131I therapy among patients with thyroid cancer.