Background: mEOCs are an uncommon subset of epithelial ovarian cancers. Most patients have early stage disease at presentation and a good prognosis. However, patients with advanced stage disease at diagnosis are rare and can be difficult to distinguish from gastrointestinal metastases to the ovary. They have a poor prognosis and a low response to standard platinum /taxane chemotherapy. Rather than assigning chemotherapy according to the tissue of origin, selecting treatment based on the molecular characteristics of mEOC should be explored. Molecular profiling of mEOCs may help identify patients for clinical trials with targeted/novel therapies. Methods: 304 mEOCs referred to Caris Life Sciences (from 2009 - 2014) were evaluated. The diagnosis was based on reported pathology. Specific testing was performed per physician request and included a combination of sequencing (Sanger, NGS or pyrosequencing), protein expression (IHC), gene amplification (CISH or FISH), and/or RNA fragment analysis. Results: Alterations in the MAP Kinase pathway were common in mEOCs with the most frequent mutations observed in KRAS (49%). The mutation rate in BRAF was 3.5%. Alterations in the mTOR pathway occurred at a less frequent rate (PIK3CA 12% and PTEN 6%). PD-1 positivity was observed in 43% of tumor infiltrating lymphocytes and PD-L1 was positive in 14% of mEOCs. cMET overexpression was seen in 33% of cases, but no cMET amplification was seen. HER2 amplification (per ASCO-CAP guidelines) by FISH was observed in 11%. EGFR amplification occurred in 50% of cases and 57% had overexpression of EGFR by IHC.35% of mEOCs tested (37 of 105 cases) had P53 mutations. P53 mutated (n = 37) and wildtype (n = 68) mEOCs differed significantly in ER, PR and HER2 expression and BRAF, PIK3CA and PTEN mutation prevalence. Conclusions: Molecular profiling highlights the genomic heterogeneity and distinct molecular subsets in mEOCS and demonstrates the similarities with mucinous gastrointestinal cancers. There are a number of potential treatment targets and therapeutic options that could be investigated in phase 2 basket trials. Given the rarity of advanced stage mEOCs this will require international collaboration.