Mouse models of human cancers may provide a valuable resource for the discovery of cancer biomarkers. We have developed a practical strategy for profiling specific proteins in mouse plasma using low-volume sandwich-immunoassays. We used this method to profile the levels of 14 different cytokines, acute-phase reactants, and other cancer markers in plasma from a mouse models of intestinal tumors and their wild-type littermates, using as little as 1.5 microliters of diluted plasma per assay. Many of the proteins were significantly and consistently up-regulated in the mutant mice. The mutant mice could be distinguished nearly perfectly from the wild-type mice based on the combined levels of as few as three markers. Many of the proteins were up-regulated even in the mutant mice with few or no tumors, suggesting the presence of a systemic host response at an early stage of cancer development. These results have implications for the study of host responses in mouse models of cancers and demonstrate the value of a new low-volume, high-throughput sandwich-immunoassay method for sensitively profiling protein levels in cancer.