Secreted phospholipases A(2) (sPLA(2)s) have recently been associated with several cancers, but their role in breast cancer is unknown. Here we demonstrate that mRNA expression of group IIA, III and X sPLA(2)s differs both in vivo in tumour biopsies and in breast cancer cells in vitro. Their expression is differentially regulated by DNA methylation and histone acetylation and, significantly, all three genes are silenced in aggressive triple negative cells due to both mechanisms. The transcription start site promoter region and the upstream CpG islands, exclusive to the group X sPLA(2) gene, have variable roles in the regulation of sPLA(2) expression. Our results suggest that the differential expression of hGIIA, hGIII and hGX sPLA(2)s in breast cancer cells is a consequence of various degrees of epigenetic silencing due to DNA hypermethylation and histone deacetylation. (C) 2014 Elsevier Inc. All rights reserved.