OBJECTIVE: Intratumor clonal heterogeneity limits efficacy and duration of response to targeted treatments in metastatic cancer. About 50% of colorectal cancer patients have such distant metastases, accounting for virtually all deaths from the disease. We followed a patient with metastatic colon carcinoma who had undergone several surgeries after being diagnosed with colorectal cancer in 2006 and had survived for over 10 years. STUDY DESIGN: We characterized 5 tumor biopsies and 1 plasma sample collected at clinical follow-up using high throughput sequencing. RESULTS: Serial changes in circulating levels of subclonal private mutations correlated with different treatment responses between metastatic sites. CONCLUSION: This comparison of biopsy and plasma sample in a single patient with metastatic colorectal cancer shows that circulating tumor DNA can allow realtime sampling of multifocal clonal evolution. Through our research, we hope the information of the mutations in this patient would assist studying the relationship between mutations and survival. © Science Printers and Publishers, Inc.