To analyze the frequency of and hotspot mutations in circulating tumor DNA (ctDNA) from patients with metastatic colorectal cancer (mCRC). Observational, descriptive and retrospective study in mCRC patients with available ctDNA-based genotype of , and . The frequencies of plasma mutations for , and were 34% (± 7), 4% (± 3) and 4% (± 3), respectively. Median overall survival of plasma-tested -mutated patients was 26.6 months (95% CI: 14.4-not estimable [NE]), while wild-type patients did not reach the median survival during follow-up. Median progression-free survival for wild-type and -mutated patients was 12 (95% CI: 7-NE) and 4 months (95% CI: 4-NE), respectively. Our work supports the utility of , and analysis in liquid biopsy from mCRC patients.