Alterations in gene sequences, expression levels, and protein structure or function can be used as 'molecular markers' to detect cancers at an early stage, determine prognosis, and monitor disease progression or therapeutic response. DNA-based markers of cancer include mutations, loss-of-heterozygosity, microsatellite instability, DNA hypermethylation, mitochondrial DNA mutations and detection of viral DNA. There are various ways of detecting cancer cells by analysing RNA. Techniques to identify alterations in protein structure or function that are associated with cancer include antibody-based detection methods, measurement of enzymatic activity and two-dimensional gel analysis of samples. New approaches to discovering molecular markers include microarray analysis, serial analysis of gene expression and proteomic technologies. Clinical researchers should design future trials to incorporate plans for collecting and analysing molecular markers. Molecular biologists should take advantage of the number of tumour samples now available in tissue banks to identify new molecular markers and to more fully assess existing ones.