The specific role of ERβ isoforms in CRC is yet to be fully elucidated; however, it is plausible that the co-expression of different isoforms of the receptor (namely ERβ2 and ERβ5), even in the presence of low levels of full-length ERβ, would complicate the estrogen-mediated signaling involved in tumor suppression, and therefore, this needs to be taken into account when designing therapeutic strategies targeting the estrogen pathway. Here, ESR2 is linked to colorectal carcinoma.