BACKGROUND.Recently, there has been considerable interest in neoadjuvant chemotherapy for colorectal liver metastases. However, there is little information that defines how much liver should be removed after a favorable response.METHODS.Liver metastases from 2 groups of patients were analyzed: 25 metastases were evaluated from a group that did not receive chemotherapy and 26 lesions were studied from patients who had received systemic chemotherapy before resection. All patients except for 1 had 5‐fluorouracil (5‐FU), leucovorin (LV), and irinotecan (CPT‐11); 1 had 5‐FU and LV alone. The average duration of chemotherapy was 2.9 ± 0.7 months. Separate assessments of the histopathologic features of the central and peripheral portions of each tumor were made. The pathologist was blinded to all clinical information.RESULTS.All of the untreated metastases had well‐circumscribed borders. Irregular borders were seen in 6 of the postchemotherapy lesions (26%), which was particularly prominent in lesions that had significantly contracted. After chemotherapy, discrete islands of viable tumor cells outside of the main tumor mass were seen in 4 patients, but all were close to the peripheral margin of the tumor mass. Viable tumor cells were more frequent in the periphery of metastases, regardless of chemotherapy exposure. Central necrosis was prominent in untreated metastases, but disappeared after chemotherapy. In lesions treated with chemotherapy, central fibrosis was greater compared with untreated lesions.CONCLUSIONS.After a partial response to chemotherapy, liver metastases shrank in a generally concentric fashion. These findings support the practice of removing less liver after downsizing with chemotherapy. Cancer 2008. © 2007 American Cancer Society.