In 3D cultures, breast epithelial cells form lobular acini that structurally resemble breast alveoli in vivo. Enlarged acini with modified acinar morphology are characteristic of transformed and/or cancer breast cells. A genome-wide miRNA expression screen comparing non-transformed and tumorigenic MCF10A cell lines identified miR-205 as a potential modifier of acinus size. In support of this hypothesis, miR-205 was found overexpressed in transformed and tumorigenic MCF10 cells. We showed that forced expression of miR-205 in non-transformed MCF10A cells increased the size of acini, whereas miR-205 antisense oligonucleotides restored a normal morphology. MiR-205 did not modify cell proliferation but rather inhibited apoptotic cell death. Moreover, miR-205 targets ZEB1, an inhibitor of E-cadherin. E-cadherin was induced upon miR-205 overexpression. Downregulating E-cadherin restored normal acinar morphology in miR-205 expressing cells, consistent with E-cadherin being involved in the miR-205-dependent acini phenotype.