A biopsy device includes an instrument set and an instrument drive unit removably coupled to the instrument set. The instrument set includes an instrument set housing; an elongate outer cannula having a tissue receiving aperture in a side wall thereof; an elongate inner cannula disposed within an outer cannula lumen; an aspiration vent fluidly coupling the outer cannula lumen to atmosphere; and an aspirate valve in the aspiration vent, and configured such that the outer cannula lumen is vented to atmosphere only when the aspirate valve is open. The instrument drive unit includes a drive unit support structure removably coupled to the instrument set housing; a motorized inner cannula driver configured to axially oscillate the inner cannula relative to the outer cannula to sever tissue extending through the tissue receiving opening; and an actuating member configured to selectively mechanically prevent the aspirate valve from closing.