Chromosomal aberrations involving the chromosomal breakpoint region 12q14-15 are frequently seen in a variety of mesenchymal tumors as uterine leiomyomas, lipomas, myxoid liposarcomas, enchondromas, or hemangiopericytomas. Therefore, this breakpoint region seems to be one of the most frequent chromosomal abnormality associated with the initiation of human mesenchymal neoplasms. To narrow down the breakpoint region on a molecular level in cells of three pulmonary chondroid hamartomas with 12q14-15 aberrations, we performed fluorescence in situ hybridization analysis with different cosmid clones originating from a YAC and cosmid contig overspanning parts of the region 12q14-15. We were able to narrow down the breakpoint to a region of 175 kb belonging to an area designated multiple aberration region because it also includes the breakpoints of leiomyomas, lipomas, and pleomorphic adenomas with 12q14-15 abnormalities. Our molecular and cytogenetic data suggest that hamartomas of the lung molecularly belong to the benign group of mesenchymal tumors showing multiple aberration region involvement.