The Ki-67 protein was isolated twenty-five years ago and has become the first histological marker of proliferating cells until now. This molecule with a unique structure possesses such fundamental biological functions that are essential for normal cell proliferation. Since the Ki-67 protein is present in every dividing cell (G1, S, G2/M phase) but is absent from the resting cells (G0 phase) it is very much suitable for identifying the proliferating fraction of cells. Thus, it provides essential information concerning the malignancy of a tumor and about the prediction of response to a certain therapy. Based on its important role in cell proliferation, the Ki-67 protein might also play a role in tumor genesis. In their present work the authors discuss the history and the properties of Ki-67, its role in cell cycle regulation and its prognostic importance in different malignant disorders.