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Loss of heterozygosity on chromosome 16q region is shown to occur frequently in breast cancers regardless of difference in phenotype or extent of tumor spread, and inactivation of tumor-suppressor genes located on the region is considered to be involved in the acquisition of malignant phenotype of mammary glandular epithelial cells. Intracystic papillary carcinoma of the breast is diagnostically important entity because of the difficulty of differential diagnosis from intraductal papilloma preoperatively. Indeed, intracystic papillary carcinoma is usually of low-grade histologic atypia (Grade 1), and its well differentiated nature is biochemically supported by high estrogen-receptor and progesterone-receptor value in their tissue extract. Among intracystic papillary tumors of the breast, LOH on chromosome 16q was detected in 71% of intracystic papillary carcinoma, whereas it was absent in intraductal papilloma by both of Southern blot analysis and microsatellite polymorphism analysis mediated by polymerase chain reaction. Therefore, LOH on chromosome 16q was suggested to be helpful for differential diagnosis of intracystic papillary tumors and to be applicable to the materials of fine needle aspiration performed preoperatively.