Rearrangements of chromosome region 12q14-15 affecting the HMGIC gene are a frequent finding in benign solid tumors. Another non-random chromosomal alteration observed in subgroups of several of the tumor entities with 12q14-15 changes are rearrangements of 6p21 resulting in alterations of the HMGIY gene, which have so far not been documented in pleomorphic adenomas of the salivary glands. In our series of 335 pleomorphic adenomas, karyotypic changes affecting chromosomal region 6p21-23 were observed in five tumors all showing either a simple or complex t(6;8)(p21-p23;q12). Molecular cytogenetic studies of two of these tumors revealed that the 6p-breakpoint of this translocation maps distal to HMGIY, not affecting the gene or its closer vicinity. The results strongly suggest that pleomorphic adenomas are the only exception to the rule that entities of benign tumors with HMGIC rearrangements also have subtypes with HMGIY rearrangements. The difference from the other tumors is discussed in terms of tissue specificity of both HMG protein genes.