The gold standard for clinical outcome of most cancers has been the clinical and pathologic staging of the tumors after surgery. For colorectal cancer (CRC), nodal involvement at the time the primary tumor is resected has been the most reliable indicator of clinical outcome; however, recently, combinations of molecular markers have been reported to be equivalent to pathologic or clinical staging in predicting clinical outcome. In addition, molecular markers can be used in conjunction with clinical or pathologic staging to provide a stronger indicator of clinical outcome than staging alone. We propose that "molecular staging" be added to pathologic staging to aid in predicting clinical outcome and making therapeutic decisions for colorectal cancers, especially stage II and III CRCs. We have reported that the clinical usefulness of most molecular markers varies with the ethnic group of the patients and the anatomic location of CRCs; this complicates the evaluation of prognostic biomarkers and requires much larger numbers of cases to be evaluated. Nevertheless, nuclear accumulation of p53 (p53nac) and phenotypic expression of Bcl-2, MUC-1 and p27kip-1 may be molecular markers approaching acceptance for use in molecular staging of specific subgroups of colorectal cancers. © 2002 Wiley-Liss, Inc.