Case 1 was a 58-year-old woman diagnosed with unresectable liver metastases from advanced rectal cancer. We performed laparoscopic low anterior resection for sigmoid cancer. As the first-line treatment, FOLFOX+bevacizumab(BV)was applied for 16 courses. The second-line treatment, FOLFIRI plus BV, was applied for four courses. However, the disease progressed with worsening liver metastases. The sequencing of K-RAS genes from the biopsy specimens of sigmoid colon cancer revealed an expression of a wild-type K-RAS. As the third-line treatment, panitumumab was applied. After 8 courses of this chemotherapy regimen, a significant reduction in the size of liver metastases was observed. Case 2 was an 81-year-old man diagnosed with unresectable liver metastases from advanced rectal cancer. We obliged the patient by performing laparoscopic rectal resection. As the first-line treatment, XELOX plus BV was applied for 10 courses. As the second-line treatment, IRIS was applied for 6 courses. However, this failed to prevent him from having a progressive disease. As the third-line treatment, panitumumab was applied for 2 courses, and a significant reduction in the size of liver metastases was observed. Our findings suggested that panitumumab has great potential for effective treatment of patients with unresectable stageIV colorectal cancer.