Using an expression level threshold of −4.5, we found that low expression levels of the ERβ1 and ERβ5 isoforms (transcript variants a and g: primer pair 2) were independent factors associated with sporadic colorectal cancer recurrence (ERβ > −4.5 presented a 4.08-fold higher risk of relapse (CI 1.69–9.84); p = 0.002). Here, ESR2 is linked to colorectal cancer.