The negative impact of regional lymph node metastasis on survival from nonmetastatic colorectal cancers is proportional to the number of nodes harvested. A thorough lymph node examination by the pathologist is essential for accurate staging. Recommendations in the USA and Europe stipulate that a minimum of 12–15 lymph nodes must be examined to accurately predict regional node negativity. The prognostic separation for stage III colorectal cancer obtained by the lymph node ratio is superior to that of the absolute number of positive nodes. The extent of mesenteric resection, pathologic technique, age or tumor location may influence lymph node yield. In the future, biological significance and clinical impact on outcome of very small amounts of tumor in regional nodes could help in staging patients. The current data are considered insufficient to recommend either the routine examination of multiple tissue levels of paraffin blocks or the use of special/ancillary techniques.