Rationale:Primary leiomyosarcoma (LMS) of the vein is a rare tumor that arises from the smooth muscle cells of the vessel wall and has an extremely poor prognosis. This tumor can occur in vessels such as the inferior vena cava, great saphenous vein, femoral vein, iliac vein, popliteal vein, and renal vein; the inferior vena cava is the most common site. LMS of the femoral vein can result in edema and pain in the lower extremity; therefore, it is not easy to be differentiated from deep vein thrombosis (DVT). Moreover, virtually no studies have described the ultrasonographic features of LMS of the vein in detail.Patient concerns:We present a case of a 55-year-old woman with LMS of the left femoral vein that was misdiagnosed as having deep vein thrombosis (DVT) on initial ultrasonographic examination. The patient began to experience edema and pain in her left leg seven months previously. She was diagnosed as having DVT on initial ultrasonographic examination, but the DVT treatment that she had received for 7 months failed to improve the status of her left lower limb.Diagnoses:She subsequently underwent re-examination by means of a multimodal ultrasonographic imaging approach (regular B-mode imaging, color Doppler imaging, pulsed-wave Doppler imaging, contrast-enhanced ultrasonography), which confirmed a diagnosis of LMS.Interventions:This patient was treated successfully with surgery.Outcomes:This case demonstrates that use of multiple ultrasonographic imaging techniques can be helpful to diagnose LMS accurately. Detection of vasculature in a dilated vein filled with a heterogeneous hypoechoic substance on ultrasonography is a sign of a tumor.Lessons:The pitfall of misdiagnosing this tumor as DVT is a useful reminder.