Surgical resection is the primary treatment modality for colorectal cancer, and the pathologic assessment of the resection specimen provides data that is essential for patient management, including the estimation of postoperative outcome and the rationale for adjuvant therapy. The essential elements of the pathological assessment of colorectal cancer resection specimens include the pathologic determination of TNM stage, tumor type, histologic grade, status of resection margins, and vascular invasion. The prognostic and/or predictive value of these elements, as well as guidelines for their derivation and interpretation, are reviewed in detail. Other tissue-based prognostic factors that are strongly suggested by existing data to have stage-independent prognostic value or to predict response to adjuvant therapy but that have not yet been validated for routine patient care are also reviewed. These include perineural invasion, tumor border configuration, host immune response to tumor, and molecular features such as microsatellite instability or loss of heterozygosity of chromosome 18. The need for high-quality, reproducible pathologic data in the care of the colorectal cancer patient, and the dependence of that data on standardization of all aspects of pathological assessment, is emphasized.