Abstract: Methods and compositions are provided for diagnosing colorectal cancer in a mammalian subject, preferably in a serum or plasma sample of a human subject. The methods and compositions enable the detection or measurement in the sample or from a protein level profile generated from the sample, the protein level of one or more specified biomarkers. Comparing the protein level(s) of the biomarker(s) in the subject's sample or from protein abundance profile of multiple biomarkers, with the level of the same biomarker(s) or profile in a reference standard, permits the determination of a diagnosis of colorectal cancer, or the identification of a risk of developing colorectal cancer, or enables the monitoring of the status of progression or remission of colorectal cancer in the subject followed during a therapeutic protocol.