Lymph node status is the strongest prognostic factor for survival in colorectal cancer. There are several guidelines concerning the minimum numbers of lymph nodes that need to be examined to make reliable staging possible, but there is no consensus in the available literature. In this study, we determine in patients with rectal cancer factors that relate to the number of lymph nodes found and the presence of lymph node metastasis. In addition, the number of examined lymph nodes was correlated with prognosis. A total of 1227 patients were selected from a multicenter prospective randomized trial investigating the value of neoadjuvant radiotherapy. The median number of examined lymph nodes in all patients was 7.0. The number of retrieved lymph nodes in patients with node metastasis was significantly higher than in node negative patients. After neoadjuvant radiotherapy fewer lymph nodes were retrieved (6.9 vs. 8.5; P<0.0001). Variations in lymph node yield between pathology laboratories and individual pathologists were striking. The following patient and tumor characteristics are associated with a significant lower lymph node retrieval: age over 60 years, overweight, small size, and low invasion depth of the tumor, poor differentiation grade, and absence of a lymphoid reaction. Node negative patients in whom seven or less lymph nodes were examined had a lower recurrence free interval than patients in whom at least 8 lymph nodes were examined (17.0% vs. 10.7%, P=0.016). We conclude that in pathology laboratories a median of at least 8 lymph nodes need to be examined in rectal cancer specimens, but that higher numbers are desirable and achievable in most cases, even after preoperative radiotherapy.