To date, no histopathologic criteria have been established to describe treatment response after neoadjuvant chemotherapy in ovarian cancer. The aim of this study was to identify histopathologic features of tumor regression in ovarian cancer specimens obtained after neoadjuvant chemotherapy regarding their ability to indicate treatment response. This study systematically evaluated histopathologic features of tumor regression in advanced-stage ovarian cancer treated with neoadjuvant chemotherapy (n = 49) and in a control group treated with primary surgery (n = 35). In addition, the largest tumor size was measured in the surgical specimens. Overall survival served as the reference standard with a median follow-up of 49 months. There was a significantly higher presence of regressive changes in the postchemotherapy group compared with the untreated control group (P < or = .04). The presence of scattered solitary tumor cells, fibrosis, foamy macrophages, and giant cells of foreign-body type each indicated previous neoadjuvant chemotherapy with high specificity (80.0%-100%) but with low sensitivity (18.4%-63.3%). Inflammatory cell infiltrates, isolated psammoma bodies, and hemosiderin were also associated with previous chemotherapy but with lower specificity. The presence of necrosis was significantly correlated with larger tumor size within the specimens (rho = 0.5, P < .0001) and was more often found in the control group. For both groups, the extent of regressive changes, evaluated as a single parameter or in combination, showed no correlation with overall survival. However, patients with absence of residual tumor, scattered solitary tumor cells, or residual tumor foci of 5 mm or less after neoadjuvant chemotherapy had a significantly longer median overall survival of 45.6 versus 27.3 months in patients with larger tumors (P = .02). Various histopathologic features generally associated with posttreatment changes did not allow differentiation of responding from nonresponding patients and provided no prognostic information. The residual tumor size after neoadjuvant chemotherapy was the only criterion significantly correlated with treatment response and subsequent overall survival.