The tissue kallikrein family represents the largest cluster of contiguous proteinase genes in the entire human genome. Its 15 members are expressed primarily in a tissue-specific manner, but can also be detected in biological fluids such as serum and seminal plasma. The mature active tissue kallikreins play vital roles in numerous physiological and pathological processes, in which they are able to function individually or in cascade pathway(s). Their genetic polymorphisms, alternative splicings and aberrant amounts of transcripts and/or proteins are often correlated with increased cancer risk, thus providing a sensible application for the use of tissue kallikreins as diagnostic, prognostic and predictive tumour markers. In this review, an updated overview of scientific research and patents regarding the functional features and clinical indications of tissue kallikreins in neoplastic diseases is provided.