Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic stem cell disorder that causes clonal expansion of glycosylphosphatidylinositol (GPI) anchor–deficient cells. A somatic mutation of PIG-A that encodes a subunit of the enzyme complex in GPI anchor synthesis results in deficiency of GPI-anchored proteins on the surface of the blood cell. The mechanisms of clonal expansion of abnormal hematopoietic stem cells are unclear. We found a patient with the disorder having chromosomal abnormality 46XX, t(12; 12)(q13; q15) in all cells bearing a mutation of PIG-A and only in those cells, suggesting that the translocation may be causally related to clonal expansion. We mapped the breakpoints to clone genes that may be involved in the pathogenesis of this disease. Because the patient did not have GPI anchor–deficient lymphocytes, it was difficult to establish GPI anchor–deficient cell lines. We constructed somatic cell hybrids by fusing GPI anchor–deficient monocytes to mouse myeloma cells deficient in hypoxanthine phosphoribosyltransferase and selected hybrids carrying chromosome 12 by monitoring the expression of human CD9. We chose hybrids carrying chromosome 12 with deletion or duplication of the q13–q15 region by analyzing microsatellite markers. We mapped the breakpoints between WI-9630 and CHLC.ATA29H01 in q13 and between D12S355 and sts-N34486 in q15 using the hybrids carrying the deleted chromosome 12. We designed new sequence tagged site markers around D12S355 and fine-mapped the breakpoint in q15 within a distance of 2 kilobase pairs. The breakpoint in q13 was determined by the inverse polymerase chain reaction using primers near the breakpoint in q15.