A total of 45 patients, after surgical resection of colorectal liver cancer metastases, were retrospectively analyzed to define areas of failure, to identify some possible prognostic factors (site of primary, stage, site, number of metastases, preoperative carcinoembryonic antigen, differentiation of the primary, type of surgery), and to seek a new rationale for a multimodal approach. The median postoperative follow-up was 18 months (range: 4-45 months). Survival rate was calculated by the actuarial method, and statistical significance was tested by the Mantel-Haenszel test. Twenty-eight patients had a relapse. These recurrences were hepatic in 11 patients, extrahepatic (intra- and extra-abdominal) in 12 patients, and intra- and extrahepatic in five patients: The stage (classification of the Istituto Nazionale Tumori of Milan) was the most important parameter related to the overall recurrence rate (47% in stage I, 62% in stage II, and 81% in stage III) and to the overall and disease-free survival. Stage was significantly related to hepatic relapse but not to extrahepatic relapse. In stage I the failure rate of 18 months was similar in hepatic and extrahepatic relapses (one third to one fourth of the patients); in stages II and III the hepatic failure rate was always higher than the extrahepatic rate. These data indicate that surgery alone is an inadequate form of therapy in cases of colorectal cancer metastases of the liver, and an adjuvant therapy, including alternate regimens of intraperitoneal and systemic chemotherapy, should be considered.