A highly sensitive allele specific polymerase chain reaction was developed and applied to the detection of K-ras mutation in human colon tumor cells both in the blood and in tissues. An experimental model of human colon carcinoma cells, carrying a GAT mutation in the 12th codon of the K-ras gene, and grafted into nude mice has been selected for evaluating the occurrence of cells in the course of disseminating into the host. We have found tumor cells circulating in the blood starting 37 days following subcutaneous primary implantation. Occasional micrometastatic deposits could be detected in lymph node draining the xenograft, but no tumor cells were found in lungs and mediastinum. In this experimental model, our results indicate that the mere presence of tumor cells in the blood does not imply the full accomplishment of the multi-step metastatic process.