BACKGROUND: After chemotherapy, complete clinical responses of colorectal liver metastases (CRLMs) increasingly occur, but these responses are rarely complete pathological responses. The management of patients with missing metastases, that is, CRLMs that disappear under chemotherapy are undetectable intraoperatively and finally left in place, continues to be controversial. The aim of this study was to assess the long-term outcome of patients with "missing CRLMs." PATIENTS: Between 1999 and 2007, among 523 patients operated on for CRLMs, 96 missing CRLMs were observed and left in place in 27 originally unresectable patients. All of these patients received preoperative chemotherapy. Hepatic arterial infusion (HAI) of oxaliplatin combined with systemic 5-fluorouracil was administered in 23 patients, including 12 before hepatectomy and 11 after. Hepatic surgery was performed after a minimal interval of 3 months during which CRLMs had disappeared on imaging. RESULTS: After a median follow-up of 55 months (24-137) after hepatic surgery, an intrahepatic recurrence was diagnosed in 14 (52%) patients, but the recurrence rate was significantly lower in patients who had received adjuvant HAI compared with the others (27% vs 83%, P = 0.006). Recurrences arose at the site of the missing CRLMs in 9 (33%) patients, but was associated in all cases with another recurrence in the liver. The 5-year overall survival rate of these 27 highly chemosensitive patients was 80%, and the 5-year disease-free survival rate was 23%. CONCLUSION: Highly chemosensitive patients, whose initially unresectable CRLMs become resectable because of missing CRLMs left in place, have a favorable long-term outcome. Missing CRLMs should not be longer, a contraindication to hepatic surgery. Use of postoperative HAI of oxaliplatin can help to reduce the risk of hepatic relapse.