Abstract Objective To evaluate the efficacy and tolerability of imatinib mesylate in patients with recurrent low-grade serous carcinoma (LGSC) of the ovary, peritoneum, or fallopian tube. Methods This open-label, single-institution phase II trial enrolled patients with platinum-resistant LGSC who had measurable disease, had received up to 4 platinum- and/or taxane-containing chemotherapy regimens, and had been previously screened for at least one imatinib targeted biomarker (c-kit, platelet-derived growth factor receptor [PDGFR]-β, or bcr–abl). Imatinib (600mg) was administered daily for one 6-week course and continued in the absence of toxicity and disease progression. Results Thirteen patients were enrolled; 12 were evaluable for toxicity, and 11 were evaluable for response. A total of 17 courses were administered (median, 1 course; range, 1–5 courses). Complete or partial responses were not observed. One patient had stable disease for 7.3months. c-Kit, bcr–abl, or PDGFR-β were present in 48%, 77%, and 100% of patients, respectively. No correlation between best response (stable disease) and the presence of imatinib-targeted biomarkers was observed. Adverse events included grade 3 skin rash in one patient leading to discontinuation of the drug, and grade 3 febrile neutropenia and grade 2 weight gain in two patients leading to dose reductions. The most common grade 1 or 2 toxicities were fatigue (66%), nausea/vomiting (66%), and diarrhea (41%); grade 3 toxicities included skin rash and granulocytopenia events. No grade 4 or 5 toxicities were observed. The median progression-free survival time was 1.3months (95% CI, 1.27, 1.40months), and the median overall survival time was 14.9months (95% CI, 11.0, 18.9months). Conclusion Imatinib is well-tolerated but has no activity in patients with platinum- and taxane-resistant LGSC or the ovary, peritoneum, or fallopian tube.