Characterization of gross chromosomal rearrangements, particularly translocations in neoplasms, has proven to be valuable in patient management by aiding in diagnosis, defining prognosis, and leading to new therapeutic interventions. In this report, we investigate two apparently balanced translocations, t(6;17)(q23.3;p13.3) and t(2;13)(p21;q14.11), in patients with myeloid neoplasms and uncover concomitant microdeletions associated with the breakpoints. Breakpoint mapping by fluorescence in situ hybridization (FISH) detected deletions at or adjacent to all breakpoints. Subsequently, array comparative genomic hybridization on the 244 K Agilent platform refined the deletion boundaries, revealing a 1.7 Mb deletion directly adjacent to the 6q23.3 breakpoint, and a 562 kb deletion at 17p13.3 in the first case. The second case was found to harbor a 195 kb deletion at 2p21 and a 1.4 Mb deletion distal to the 13q breakpoint at 13q14.3. Additionally, a 133 kb deletion within the breakpoint region at 13q14.11 and a 265 kb deletion proximal to the breakpoint were discovered, neither of which was detected by FISH. Although a gene fusion resulting from either novel rearrangement cannot be determined from these data, formation of a fusion transcript cannot be excluded because the resolution of the techniques used does not allow definite delineation of the breakpoint locations. Although the incidence and clinical relevance of these focal imbalances remains to be evaluated, the cases presented here support high resolution evaluation of presumably balanced rearrangements in neoplasms. Such imbalances may portend important hitherto unrecognized prognostic and diagnostic categories.