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Accumulated data implicate the fimbria as a site of origin and descriptive molecular pathology and experimental evidence strongly support a serous carcinogenic sequence in the Fallopian tube. Both direct and indirect (\u2018surrogate\u2019) precursors suggest that the benign tube undergoes important biological changes after menopause, acquiring abnormalities in gene expression that are often shared with malignancy, including <jats:italic><jats:styled-content style=\"fixed-case\">PAX2<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">ALDH1<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">LEF1<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">RCN1<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">RUNX2<\/jats:styled-content><\/jats:italic>, beta\u2010catenin, <jats:italic><jats:styled-content style=\"fixed-case\">EZH2<\/jats:styled-content><\/jats:italic>, and others. However, the tube can be linked to only some <jats:styled-content style=\"fixed-case\">HGSCs<\/jats:styled-content>, recharging arguments that nearby peritoneum\/ovarian surface epithelium (<jats:styled-content style=\"fixed-case\">POSE<\/jats:styled-content>) also hosts progenitors to this malignancy. A major sticking point is the difference in immunophenotype between <jats:styled-content style=\"fixed-case\">POSE<\/jats:styled-content> and M\u00fcllerian epithelium, essentially requiring mesothelial to M\u00fcllerian differentiation prior to or during malignant transformation to <jats:styled-content style=\"fixed-case\">HGSC<\/jats:styled-content>. However, emerging evidence implicates an embryonic or progenitor phenotype in the adult female genital tract with the capacity to differentiate, normally or during neoplastic transformation. Recently, a putative cell of origin for cervical cancer has been identified in the squamo\u2010columnar (<jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>) junction, projecting a model whereby Krt7+ embryonic progenitors give rise to immunophenotypically distinct progeny under stromal influences via \u2018top down\u2019 differentiation. Similar differentiation can be seen in the endometrium with a parallel in juxtaposed mesothelial and M\u00fcllerian differentiation in the ovary. Abrupt mesothelial\u2013M\u00fcllerian transitions remain to be proven, but would explain the rapid evolution, short asymptomatic interval, and absence of a defined epithelial starting point in many <jats:styled-content style=\"fixed-case\">HGSCs<\/jats:styled-content>. Resolving this question will require accurately distinguishing progenitor from progeny tumour cells in <jats:styled-content style=\"fixed-case\">HGSC<\/jats:styled-content> and pinpointing where initial transformation and trans\u2010differentiation occur, whether in the tube or <jats:styled-content style=\"fixed-case\">POSE<\/jats:styled-content>. Both will be critical to expectations from prophylactic salpingectomy and future approaches to pelvic serous cancer prevention. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. 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