Colorectal metastases in the liver grow according to three histological patterns: a pushing pattern, a replacement pattern, and a desmoplastic pattern. The objective of the current study was to explore the prognostic significance of these three growth patterns for survival. The study included 217 consecutive patients, liver resected between 2007 and 2011 due to hepatic metastases from colorectal adenocarcinoma. The growth patterns were assessed on archival hematoxylin and eosin-stained tissue sections. In 150 metastases, the density of the immune cell infiltrate at the tumor periphery was judged by a semi-quantitative method. The prevalence of the pushing-type, the desmoplastic-type, and the replacement-type was 33%, 32%, and 11%, respectively; 24% of the metastases displayed a mixed pattern. Kaplan-Meier analysis and Cox regression demonstrated a prognostic significance of the growth patterns (P=0.0006, log-rank test), as the replacement pattern appeared as an independent predictor of poor overall survival. For patients with replacement growth, the hazard of death was 2-2.5 times higher than for patients with pushing growth (P=0.004, cox regression) or mixed growth (P=0.01), and nearly four times higher than for patients with desmoplastic growth (P<0.0001). The negative prognostic effect of the replacement growth pattern was even more pronounced after adjusting for tumor size. Desmoplastic growth corresponded with small tumor size, dense lymphocytic infiltration and a more favorable prognosis. Eventually, the growth patterns may contribute to a histology-based prognostic biomarker for patients with colorectal liver metastases.Modern Pathology advance online publication, 23 May 2014; doi:10.1038/modpathol.2014.4.