ERα-36, a newly described variant of the estrogen receptor alpha (ERα), is widely expressed in normal and tumor tissues. However, the functions of ERα-36 expression have not been fully revealed. ERα-36 is primarily localized to the plasma membrane and cytoplasm and has been shown to play a role in mediating non-genomic estrogen signaling. It has been demonstrated that ERα-36 is involved in cell differentiation, which could imply a key role in e.g. cancer development, nerve differentiation and immune cell maturation. Here we present a review of the recent findings in the field, especially in relation to breast cancer and the immune system, as well as the other ERs.