The aim of this study was to evaluate the significance of preoperative serum p53 antibodies (Abs) in patients with colorectal cancer. Between 2007 and 2008, serum p53 Abs were measured by enzyme-linked immunoabsorbent assay in 100 consecutive patients with colorectal cancer. Relationships between clinicopathologic features and the preoperative presence of serum p53 Abs were evaluated. Serum p53 Abs were positive in approximately 30%, regardless of the depth of tumor invasion--sm (submucosa), mp (muscularis propria), or ss (subserosa). Two patients among 23 T1 patients (9%) had lymph node metastasis. These 2 patients belonged to a group of 7 patients who were determined positive for serum p53 Abs (29%), although none of 16 patients negative for serum p53 Abs had lymph node metastasis, regardless of vascular invasion. Preoperative serum p53 Abs do not seem to be a marker of tumor progression but may be a useful marker for detecting high risk of lymph node metastasis in T1 colorectal cancer.