PURPOSE: Controversies regarding preoperative versus postoperative chemotherapy for patients having hepatic metastases of colorectal primary made us elucidate the safety of chemotherapy. By examining the histopathologic changes in the liver following preoperative chemotherapy and analyzing the relation between surgical outcomes and preoperative chemotherapy, we were able to answer whether preoperative chemotherapy is safe. METHODS: We analyzed 38 patients who underwent chemotherapy before resection of hepatic metastasis from colorectal primary, retrospectively. Types of chemotherapy regimen were FL (5-FU+leucovorin), FOLFOX4 (oxaliplatin+5-FU+leucovorin), and FOLFIRI (irinotecan+5-FU+leucovorin). Results of liver function tests were compared before and after preoperative chemotherapy. One pathologist reviewed the degree of hepatic injury from resected specimens. Associations between the histological findings of hepatic injury and surgical outcomes and chemotherapeutic agents were examined. RESULTS: Histopathologic analysis revealed severe liver injury was present in 12 patients (31.6%). In further detail, moderate to severe sinusoidal dilatation was found in 3 patients (25%), steatosis of more than 30% was identified in 9 patients (75%), and steatohepatitis Kleiner score of > or =4 in 5 patients (41.7%). Preoperative chemotherapy did not affect the biochemical profiles of liver function. The overall perioperative complication rate was 5.3% (n=2). There was no difference in postoperative morbidity or mortality from reported results following hepatectomy. CONCLUSION: We found preoperative chemotherapy definitely induced histopathologic changes of hepatotoxicities. Even so, preoperative chemotherapy did not increase morbidity or mortality after hepatic metastasectomy. Preoperative chemotherapy seems to be safe in performing curative hepatic resection for the metastases.