Chronic granulocytic leukemia (CGL) is associated with a reciprocal translocation between chromosomes 9 and 22. The breakpoint sites on chromosome 22 are clustered in a limited region known as the major breakpoint cluster region (Mbcr). This region is approximately 5.8 Kb long and can be arbitrarily subdivided into five zones (1 through 5 from the 5' towards the 3' end) as defined by the particular sites of three restriction endonucleases. Using Southern blot analysis with two DNA probes, one spanning both the 5' and 3' regions of the Mbcr while the other only the 3' region, we mapped the precise location of the chromosomal breakpoints within the Mbcr in 62 patients with CGL and examined possible clinical correlations. There were 39 patients with 5' breakpoints (zones 1-3) and 23 patients with 3' breakpoints (zones 4 and 5). We found no correlation between the clinical phase of the disease at last followup and breakpoint distributions. The distributions of chronic phase duration (CPD) and survival were similar between patients with 5' breakpoints (median CPD = 4.0 years) and those with 3' breakpoints (median CPD = 5.2 years). Presenting clinical features and the rates of lymphoblastic transformation were also similar among the subgroups. Our data suggest that the precise location of the breakpoint within the Mbcr in CGL may not have clinical relevance.