Background and Objectives: Expression of S100A4, a small calcium-binding protein, in breast, oesophagus and gall bladder cancers is shown to be associated with adverse clinical outcome. We retrospectively examined the correlation of S100A4 expression and outcome in patients with colorectal cancer. Methods: Tissue sections from 54 patients with Dukes B, C and D cancers operated on between 1995 and 1998 were stained with anti-S100A4 antibody. The S100A4 expression profile was correlated to the clinico-pathological details. Results: There were 31 males and 23 females (mean age 65.94 years þ/À 12.29). Dukes stage, >4 positive lymph node status and S100A4 expression were significantly associated with poorer survival. The 3 years survival of patients whose tumour stained positive for S100A4 was 62.85% compared to 93.75% for those stained negative (P < 0.012). In patients with <4 involved nodes, S100A4 expression led to poorer survival (57 months vs. 74 months; P < 0.0052). Within a particular Dukes stage, S100A4 expression was associated with poorer outcome. The 5 years survival of Dukes B patients whose tumour stained negative for S100A4 was 92% compared to 54.6% for those with positive tumours. Conclusion: Our results suggest that S100A4 expression is associated with adverse clinical outcome. Inclusion of S100A4 expression status may enhance our accuracy to prognosticate in patients with colorectal cancer.