Disappearance of liver lesions during neoadjuvant chemotherapy is common and is the basis for the increasing number of patients suitable for potentially curative hepatectomy in patients with hepatic colorectal metastases. Many of the liver lesions disappearing on radiologic evaluation after successful chemotherapy for metastatic colorectal cancer are still present and alive. In patients with only some disappearing lesions, exploration should be undertaken to thoroughly evaluate all sites of previous disease. Because many small residual lesions are scars and complete pathologic responses, treatment should include not only complete treatment of all remaining lesions but also parenchymal conservation techniques such as ablations and limited resections. For patients with completely disappearing lesions, the standard therapy is still exploration and direct intraoperative assessment. However, if the patient chooses observation in the setting of negative CEA, MRI, and PET, close follow-up should be undertaken to avoid missing treatable and resectable recurrences.