If a regional lymph node taken during surgery for colorectal cancer is found to be free of tumour on histological examination this is taken to be a good sign. However, conventional staining may not be sensitive enough. Mutant-allele-specific amplification (MASA) is a technique that can detect, at the level of an individual cell, micrometastases to lymph nodes that are histologically diagnosed as negative. To examine the prognostic significance of such genetically detectable tumour cells we screened 120 colorectal cancers from patients who had no histologically detectable lymph-node metastasis at the time of surgery for mutations in K-ras (codons 12, 13, and 61) or p53 (exons 5-8). Somatic mutations were identified by MASA in 71 tumours. We next examined preserved tissues from corresponding regional lymph nodes, using MASA to look for the specific mutation found in the primary. Of 37 patients with genetically positive lymph nodes 27 had had a tumour recurrence within 5 years of surgery; none of the 34 patients who were MASA negative for lymph node metastasis had had a recurrence. Genetic diagnosis of lymph node metastasis may be a useful prognostic factor in colorectal cancer, and it could also serve as a selective marker for intensive postoperative adjuvant chemotherapy.