Background The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their relevance to disease prognosis.Methods We investigated the relevance of 19 markers in 790 patients enrolled in a large randomised trial of 5-fluorouracil using immunohistochemistry and chromogenic in situ hybridisation. The relationship between overall 10-year survival and marker status was assessed.Results Minichromosome maintenance complex component 2 (MCM2) and cyclin A were significantly associated with overall survival. Elevated MCM2 expression was associated with a better prognosis (HR=0.63, 95%CI: 0.46-0.86).Cyclin A expression above the median predicted an improved patient prognosis (HR=0.71, 95%CI: 0.53-0.95). For mismatch repair deficiency and transforming growth factor β receptor type Ⅱ (TGFBRII) overexpression there was a borderline association with a poorer prognosis (HR=0.69, 95%C/: 0.46-1.04 and HR=2.11, 95%CI: 1.02-4.40,respectively). No apparent associations were found for other markers.Conclusion This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer.