Neoadjuvant chemotherapy followed by interval debulking has become an alternative treatment option for patients with advanced-stage ovarian cancer. The effects of chemotherapy on the histologic features of the tumor have not been well described for ovarian carcinoma, especially related to changes that significantly alter the appearance of the tumor. In this study, we describe a case of ovarian serous carcinoma status-post neoadjuvant chemotherapy that showed exuberant clear cell/foamy change. This unusual morphology raised the possibility of a mixed epithelial carcinoma or a secondary malignancy. Immunohistochemical stains were performed to help distinguish whether the tumor was a serous carcinoma with chemotherapy-induced clear cell change or a distinct clear cell carcinoma of ovarian or extraovarian origin. The clear cell and conventional serous components showed diffuse positivity for CK7, CA125, and ER; however, only the clear cell component was positive for hepatocyte nuclear factor-1beta and only the conventional serous component was positive for WT1. Although there was a slight discrepancy in the staining patterns, given the lack of other typical histologic features of clear cell carcinoma, the unusual clear cell morphology was most likely the result of chemotherapy-induced changes.