AbstractAfter a diagnosis of colorectal cancer (CRC), approximately 50% of patients will present distant metastasis. Although significant progress has been made in treatments, most of them will die from the disease. We investigated the predictive and prognostic potential of APC11, the catalytic subunit of APC/C, which has never been examined in the context of CRC. The expression of APC11 was assessed in CRC cell lines, in tissue microarrays (TMAs) and in public datasets. Overexpression of APC11 mRNA was associated with chromosomal instability, lymphovascular invasion and residual tumor. Regression models accounting for the effects of well-known protein markers highlighted association of APC11 protein expression with residual tumor (odds ratio: OR = 6.51; 95% confidence intervals: CI = 1.54–27.59; P = 0.012) and metastasis at diagnosis (OR = 3.87; 95% CI = 1.20–2.45; P = 0.024). Overexpression of APC11 protein was also associated with worse distant relapse-free survival (hazard ratio: HR = 2.60; 95% CI = 1.26–5.37; P = 0.01) and worse overall survival (HR = 2.69; 95% CI = 1.31–5.51; P = 0.007). APC11 overexpression in primary CRC thus represents a potentially novel theranostic marker of metastatic CRC.