Background: Rectal gastrointestinal stromal tumors (GIST) are rare. Neo-adjuvant therapy with imatinib is recommended for locally advanced or non-resectable tumors. Case report: We report a 63 years old woman with a malignant GIST located in the recto-vaginal septum which was initially considered non-resectable. The patient was treated with imatinib as induction therapy for three months. After this lapse the tumor was successfully excised using an endo-anal approach. Due to a tumor size over 5 cm and the presence of 13 mitoses per 50 high power fields, two bad prognostic factors, treatment with imatinib was maintained for 15 months after surgery. After 20 months of follow up, the patient is free of disease with complete fecal continence and with an adequate sexual life. Secondary effects of imatinib are gradually subsiding