Objectives: The aim of this study was to examine the prognostic value of the preoperative serum α-L-fucosidase (AFU) activity in colorectal cancer and to assess whether it could add prognostic information that Dukes’ stages do not give. Methods: A postoperative follow-up of 137 colorectal cancer patients was performed, and survival analyses were carried out to evaluate the impact of AFU activity on disease-free survival. Dukes’ stage classification, preoperative serum carcinoembryonic antigen levels and six other clinicopathological features of the patients were also analysed. Results: In previous studies, we have stressed the diagnostic value of AFU activity in preoperatively obtained serum from colorectal cancer patients. In the present work, we have found that the enzymatic activity of serum AFU was not related to the Dukes’ stage of the primary tumour, but it was associated with the type of metastasis and recurrence of the disease. The mean value of preoperative serum AFU activity was higher in patients with distant metastases than in those with lymph node or peritoneal metastases, or without metastasis (p = 0.034). After a mean postoperative follow-up period of 22 months, three groups of patients with different recurrence rates could be distinguished (p = 0.0014). Similar results were found when only patients in Dukes’ stage B (p = 0.0439) or C (p = 0.0122) were considered. Conclusions: According to our findings, serum AFU activity appears to be a good prognostic factor of tumour recurrence in colorectal carcinoma. Furthermore, patients in Dukes’ stage B or C at high or very high risk of tumour recurrence could be spotted.