Current advances in cancer biology have identified major pathways involved in tumorigenesis. The association of DNA damage with premalignant stages of tumor progression, genome instability and further oncogenic transformation opens the possibility of using common DNA damage markers for early cancer detection, prediction, prognosis, therapeutics and possibly for cancer prevention. Perhaps the most sensitive DNA damage marker is gammaH2AX formation in the chromatin flanking the free DNA double-stranded ends in double-strand breaks (DSBs) and eroded telomeres, both present during oncogenic transformation. Our group and others found elevated endogenous levels of in various human cancer cell lines, premalignant lesions and solid tumors. These data suggest that increased DNA damage is a general characteristic of cancer development. GammaH2AX-based assay can be applied to human biopsies, aspirates and, possibly, to mononuclear cells of the peripheral blood. We propose that detection of gammaH2AX could benefit for the early cancer screening and to ascertain the efficiency of clinical treatment involving chemo- and radiotherapeutic protocols.