Whilst other keratins have been shown to have diagnostic or prognostic utility in ovarian cancer [27–30], limited studies to date have examined K5 and K6 expression in this malignancy. We therefore investigated the prognostic significance of KRT5 and KRT6 mRNA expression in publically available serous ovarian cancer data sets . Additionally, monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and cohorts of high grade serous ovarian carcinomas at surgery and after neoadjuvant chemotherapy. Furthermore, KRT5 and KRT6C mRNA expression was assessed in chemotherapy sensitive and chemotherapy resistant primary serous ovarian cancer cells derived from patient ascites. We also evaluated whether K5+ cells are increased in serous ovarian cancer patients following chemotherapy treatment. To our knowledge, this is the first study to investigate the relationships between KRT5 mRNA, KRT6 mRNA, K5/6, and K5 protein expression with serous ovarian cancer patient outcome.