We reported two cases of colorectal cancer patients with EGFR-positive unresectable synchronous liver metastasis effectively treated by cetuximab after the progression of the prior chemotherapy. Case 1: A 49-year-old female with unresectable synchronous liver metastasis from colon cancer received cetuximab monotherapy as fifth-line therapy. Then, abdominal CT showed shrinkage of the liver metastasis (PR) and the performance status was improved from 3 to 0 as upper abdominal pain reduced. Case 2: A 67-year-old female with unresectable liver metastasis from colon cancer received cetuximab with CPT-11 combined therapy as fourth-line therapy. After that, liver metastasis also decreased (PR), and upper abdominal pain and PS were improved from 2 to 0. These two cases of KRAS status on cancer tissue also showed wild-type, and in these cases cetuximab proved effective.