p27^kip1 is an important negatively regulator of cell cycle progression and plays a central role in the pathogenesis of a member of tumors including breast cancer. In breast cancer cells, the level of p27^kip1 expression usually decreases during tumor development and progression, in addition, cytoplasm mislocalization of p27^kip1 has been reported, but less is known about the exact molecular mechanisms. Studies have indicated that phosphorylation is the key regulation way, several signal transduction pathways are involved in the regulation of the expression and distribution of p27^kip1. To further understand the mechanism, the disparity of the interacting protein profiling between tumor cells and normal cells must be identified first. Including cyclins, cyclin-depend kinases, CRM1, jab1, SKP2, p27^kip1 has various interacting molecules. There are also several interacting molecules especially for breast cancer cells. It seems that different protein profiling cause the different expression and intracellular distribution in different cell cycle phase. So, disparity of the p27^kip1 protein profiling may be the main mechanism of its down-expression and mislocalization in breast cancer cells.