δ-Catenin is a member of the p120 catenin family. Similar to p120ctn, δ-catenin contains nine central Armadillo repeats and binds to the juxtamembrane domain (JMD) of E-cadherin. We used immunohistochemistry to detect δ-catenin expression in breast carcinoma (128 cases), and δ-catenin mRNA and protein expression was detected by reverse transcription-polymerase chain reaction and Western blotting (45 cases). The effects of δ-catenin on the activity of small GTPases and the biological behavior of breast cancer cells were explored by pulldown, flow cytometry, methyl thiazolyl tetrazolium, and Matrigel invasion assays. The results showed that δ-catenin expression increased in breast cancer tissues and was associated with a higher degree of malignancy (invasive lobular breast cancer, high tumor-node-metastasis stage, lymph node metastasis, and C-erbB-2+) and poor prognosis. Postoperative survival was shorter in patients with δ-catenin-positive expression than in patients with negative expression. δ-Catenin may regulate Cdc42/Rac1 activity, promote proliferation and invasion of breast cancer cells, and alter cell cycle progression. We conclude that δ-catenin tends to overexpress in breast carcinoma and promotes the malignant phenotype.