Biomarkers present the normal and/or disease state in humans. Genetic and epigenetic biomarkers assessed in easily accessible biological materials are useful in diagnosis, early onset or risk of developing cancer or to predict the treatment efficacy or clinical outcome of different human malignancies. Moreover, some of these markers are expressed during early stages of the tumor development and hence provide an opportunity to develop intervention and treatment strategies. Attempts are being made to validate cancer biomarkers in non-invasively collected samples. Multiplexing of clinically validated markers is still a challenge. Once validated, these markers can be utilized in clinical settings and to identify high risk populations. In this review, the current status of the clinical genetic and epigenetic biomarkers and their implication in cancer diagnosis and risk assessment are discussed. © 2006 Elsevier Ireland Ltd. All rights reserved.