The prognosis of colorectal cancer depends on the stage of the disease. However, even within the same stage there may be different outcomes in terms of recurrence and survival. Therefore, it is clear that as well as pathological stage, novel biomarkers that are capable of improving risk stratification and therapeutic decision-making are required. The present study aimed to evaluate the potential roles of two previously proposed biomarkers of tumour status: B-cell lymphoma 2 (Bcl-2) and β-catenin. A total of 412 patients undergoing surgery for primary colorectal cancer were studied. Tumour specimens of the patients were collected, fixed and processed for immunohistochemical detection of Bcl-2 and β-catenin. The data were then analyzed in relation to disease-free survival and overall survival. Pathological stage was the only variable that was significantly correlated with both disease-free and overall survival. The expression levels of neither Bcl-2 nor β-catenin were able to accurately predict prognosis. However, there was a clear association between nuclear β-catenin expression levels and disease-free survival in the three tumour stages. There was an increased hazard ratio in stage I and II nuclear β-catenin positive tumours, whereas there was a marked decrease in risk in stage III positive tumours. A similar effect was also observed with regards to overall survival, however this finding was not significant. The results of the present study suggest that conventional pathological tumour staging is the only accurate prognostic method. Neither Bcl-2 or β-catenin were shown to be useful biomarkers for the prognosis of colorectal cancer. However, the heterogeneous behaviour of nuclear β-catenin expression in the various tumour stages may indicate a possible role in predicting the response of patients to chemotherapy. Therefore, nuclear β-catenin expression may be a biomarker for the prediction of improved responses to chemotherapy.