Value of the Data •This is the first comprehensive study of the transcriptome of fish scales, an estrogen-target tissue for which information is still limited and a promising practical model for environmental pollution screening and chemical risk assessment. •The dataset has relevance for aquaculture and for toxicology/ecotoxicology/environmental studies, since altered levels of hormones (including synthetic, anthropogenic hormones) could affect the development and homeostasis of multiple marine species. •The dataset has broad applicability as it is from the European sea bass, which is a representative of the species-rich order Perciformes and an important species for marine fisheries and aquaculture. •Global transcriptomes of scales from the European sea bass, exposed for 1 and 5 days to estradiol (a natural estrogen) or genistein (a phytoestrogen) is of use for aquaculture, ichthyologists, toxicologists and comparative endocrinologists. Since estrogenic compounds and genistein can be found in aquatic environments the dataset is of use for aquaculture (e.g increased ingestion of phytoestrogens from plant-based ingredients used in fish feeds) and the comparison of genes and pathways regulated or disrupted by estradiol and genistein is of great interest for studies related to physiology, ecotoxicology/environmental studies or aquaculture in fish or other marine species. •The identified sets of differentially expressed genes in sea bass scales after exposure to estradiol or genistein provide a source of potential biomarkers for assessing exposure to estrogens, phytoestrogens or other estrogenic pollutants, and this non-invasive approach complies with the 3R principal and is under validation for environmental pollution.