Inflammatory breast cancer is a rare but highly aggressive form of locally advanced breast cancer. Inflammatory breast cancer accounts for about 5% of all cases of breast cancer. In general, women with inflammatory breast cancer present at a younger age, and in black. IBC is more likely to have metastatic disease at diagnosis, and have shorter survival than women with non-inflammatory breast cancer. The characteristic pathologic finding is dermal lymphatic invasion by carcinoma, which can lead to obstruction of the lymphatic drainage causing the clinical picture of erythema and edema. Inflammatory carcinoma of the breast has distinct biological characteristics that differentiate it from non-inflammatory carcinoma. These tumors more often have a high S-phase fraction, are high-grade, are aneuploid, and lack hormone receptor expression and her2neu overexprestion. In addition, inflammatory carcinomas are more likely to have mutations in p53 and to have high levels of vascular endothelial growth factor (VEGF) which account for tumor neovascularization and the lymphotactic process in inflammatory breast cancer. Also IBC are more likely to express E-cadherin, a trans-membrane glycoprotein that mediates cell-cell adhesion, and may contribute to the aggressive lymphovascular invasion seen in inflammatory cancers. Several genes have been identified that might contribute to the aggressive clinical behavior of inflammatory breast cancer. The overexpression of RhoC GTPase and the loss of expression of LIBC (lost in inflammatory breast cancer) were highly correlated with an inflammatory carcinoma phenotype. LIBC, a novel gene, was lost in 80% of inflammatory specimens in comparison with 21% of non inflammatory tumors. RhoC GTPase, a gene involved in cytoskeletal reorganization, was overexpressed in 90% of inflammatory tumors in comparison with 38% of non-inflammatory cancers. Furthermore, when a stable RhoC transfectant cell line was created, RhoC behaved as a transforming oncogene conferring a highly invasive phenotype similar to that seen in inflammatory breast cancer. These genes remain a promising avenue for future investigation.