Abstract: Objective To investigate the expression and clinical significance of Hedgehog related proteins in human primary breast carcinoma. Methods Tissue microarray blocks were prepared from 334 cases of breast carcinoma tissues. Immunohistochemical method was applied to analyze the expression of six Hedgehog signaling proteins, including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene Gli-1, Gli-2, and Gli-3. Results Expression of Hedgehog signaling proteins were significantly correlated with some prognostic factors, including the correlation of lymph node metastasis with the expression of Shh (P=0.001)，Gli-3 (P<0.001) and Ptch(P=0.025), the correlation of staging with Shh and Ptch expression (P=0.007 and P=0.037, respectively), the correlation of nuclear grades with Smo and Gli-3 expression(P=0.004, P=0.026), and the correlation of histologic grades with Smo expression (P=0.007). The expression of Shh, Ptch, Smo, Gli-1, Gli-2 and Gli-3 were significantly different based on phenotypes (P=0.0001, P=0.0001, P=0.004, P=0.039, P=0.031 and P=0.003 respectively). Gli-2 expression was correlated with a worse overall survival (P=0.012). Conclusion The activation of Hedgehog pathway expression is correlated with the invasiveness of breast carcinoma. Hedgehog pathway may be a useful therapeutic target for breast carcinoma. Gli-2 could be a prognostic marker.