Lysosomal cysteine proteinases, termed also cysteine cathepsins, are ubiquitous proteolytic enzymes. The most important group of their endogenous inhibitors belongs to the cystatin superfamily, which consists of three families: ste- fins, cystatins and kininogens. The involvement of cysteine cathepsins and cystatins in proteolytic processes, leading to invasion and dissemination of tumor cells, has been confirmed by the results of several in vitro and in vivo studies. These findings suggest that they play a role in the prognosis of the course of the disease and survival of cancer patients. The paper describes the biochemical properties of lysosomal cysteine proteinases and their endogenous inhibitors, as well as the role they play in the cell and in malignant tumor growth and dissemination. Cinical studies evaluating these new biological prognostic factors in cancer patients are reviewed. The results are encouraging, particularly for patients with breast cancer, but they are not yet conclusive enough to be applied in the daily clinical practice along with the already established prognostic factors.