Wnt proteins form a family of highly conserved, secreted signaling molecules that regulate cell-to-cell interactions during embryogenesis. Wnt genes and Wnt signaling are also implicated in cancer. It has been shown that Wnt proteins bind to receptors of the frizzled family on the cell surface. Through several cytoplasmic relay components including DVL-1, the human counterpart of the Drosophila disheveled gene, the signal is transduced to beta-catenin, which then enters the nucleus and forms a complex with T-cell factor (TCF) to activate transcription of Wnt target genes. We describe here the amplification of DVL-1 in 13 of 24 primary breast cancers examined, and increased expression of this gene in 11 of those tumors in comparison to corresponding non-cancerous breast tissues. Immunohistochemical staining demonstrated that DVL-1 protein was prominent in the cytoplasm of cancer cells, but not in normal epithelial cells of the mammary duct or in myoepithelial cells. These data indicate that amplification and increased expression of the DVL-1 gene may play some role in human breast carcinogenesis through derangement of the Wnt signaling pathway.