Deletions and rearrangements involving chromosome 6q have been reported in a number of human cancers such as ovarian and breast tumors as well as melanoma and hemopoietic malignancies. To gain insight into the regions undergoing deletions on the long arm of chromosome 6, we performed a survey of loss of heterozygosity (LOH) at 11 CA repeat markers, mapping from 6q13 to 6q27 in 83 matched sets of tumor and blood DNAs from breast tumor patients. LOH was observed at all tested markers with frequencies ranging from 11.4 to 39.8% of the informative cases, whereas D2S123, a marker linked to the HMSH2 gene mapping in a region rarely presenting allele losses, showed 3.2%. LOH patterns were often complex, with a number of tumors presenting multiple interstitial losses, thus indicating that chromosome 6q can be severely rearranged in breast cancer. Patterns of losses and correlation between LOH occurring at adjacent markers suggested the existence of three (possibly four) distinct regions of allele losses. These were defined by: D6S251-D6S434 (6q13), D6S292-D6S310-D6S314-D6S311 (6q24-q25), and D6S441-D6S281 (6q27). The fourth and more hypothetical region was in the 6q21 region and defined by D6S287-D6S407. Interestingly, the region at 6q24-q25 defined by D6S292-D6S310-D6S314-D6S311 was predominantly observed in evolved and aggressive breast tumors. LOH at D6S314 was correlated with PR- tumors. All together, our data suggest the possible presence of several genes on 6q whose alteration may play a role in breast cancer formation and development.