&NA;PURPOSE. Multiple attempts have been made to improve the clinical/pathologic staging system of Dukes to focus adjuvant therapy decisions. The purpose of this study was to determine whetherK‐rasmutational status of regional nodes in patients with Dukes B2colorectal cancer could be used to stage their disease more accurately.METHODS:Using formalin‐fixed, paraffin‐embedded archival material, tumor samples were screened forK‐rasmutations using a mutation‐specific polymerase chain reaction method, followed by gel electrophoresis in a 96‐well array. Patients with Dukes B2tumors that have mutations in codon 12 or 13 of theK‐rasgene were identified.RESULTS:Mutational analysis of the lymph nodes from these patients revealed an 80 percent (16/20) incidence of the same mutations in regional lymph nodes. None of the four patients with mutation‐free nodes developed recurrence compared with 37.5 percent (6/16) withK‐raspositive lymph nodes.CONCLUSIONS:The data suggest that patients with Dukes B2colorectal cancers that have mutations in codon 12 or 13 of theK‐rasgene are at high risk for the development of nodal metastases. Mutational analysis of the lymph nodes identifies high‐risk patients who should be considered for adjuvant chemotherapy. Therefore,K‐rasmutational analysis should be considered for molecular staging of colorectal cancer.