Neuroendoscopic techniques are often considered inapplicable to lesion resection because most lesions are too large for effective endoscopic resection in an appropriate time frame. To evaluate the potential of ultrasonic aspiration in neuroendoscopic procedures, the authors developed a new handpiece for endoscopic application. The instrument was subsequently tested in 10 cadaveric pig brains and applied in 5 clinical cases. In the pig brain, a precise and accurate aspiration of ventricular ependyma and brain parenchyma was obtained. Clinically, the device was applied in 3 patients with obstructive hydrocephalus, and via an endonasal transsphenoidal approach in 2 patients with pituitary macroadenomas. In all cases, the lesion was effectively aspirated without complications. Ultrasonic aspiration can be applied safely and successfully in selected endoscopic procedures. The use of this technique could expand the indications for endoscopic approaches to include intraventricular lesions and in minimally invasive transsphenoidal endonasal approaches.