Recently, the role of small heat shock proteins (HSPs) has been widely recognized in cancer research. Small HSPs are tumor-protective via numerous, independent mechanisms such as: oxidative stress protection preventing protein denaturation, anti-apoptotic activity, and likely direct suppression of the immune system. However, it is unclear whether they play any role in the initial steps in carcinogenesis. This article seeks to familiarize the reader with general characteristics of small HSPs (especially HSP-27, A/B-crystallins), tissue distribution with special regard on their expression in malignant specimens, and biological properties of intracellular HSP-27 and A/B-crystallins promoting tumor genesis and growth. A separate chapter describes immunomodulatory characteristics of extracellular HSP-27 with special emphasis on their plausible effect on the neoplasm development.