A biopsy system, comprising: (a) an instrument set, the instrument set comprising an instrument set housing, an elongate outer cannula having an axial lumen, a proximal portion coupled to the instrument set housing, and a distal portion having a tissue receiving aperture in a side wall thereof in communication with the lumen, an elongate inner cannula disposed within the outer cannula lumen, an aspiration vent fluidly coupling the outer cannula lumen to atmosphere, and an aspirate valve interposed in the aspiration vent and configured such that, when the aspirate valve is open, the outer cannula lumen is vented to atmosphere through the aspiration vent, and when the aspirate valve is closed, the outer cannula lumen is not vented to atmosphere through the aspiration vent; and (b) an instrument drive unit removably coupled to the instrument set, the instrument drive unit comprising 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 during operation of the biopsy system, such that an open distal end (28, 30) of the inner cannula moves back and forth across the tissue receiving aperture to sever tissue extending there through, and an actuating member configured to selectively mechanically prevent the aspirate valve from closing. (a) an instrument set, the instrument set comprising an instrument set housing, an elongate outer cannula having an axial lumen, a proximal portion coupled to the instrument set housing, and a distal portion having a tissue receiving aperture in a side wall thereof in communication with the lumen, an elongate inner cannula disposed within the outer cannula lumen, an aspiration vent fluidly coupling the outer cannula lumen to atmosphere, and an aspirate valve interposed in the aspiration vent and configured such that, when the aspirate valve is open, the outer cannula lumen is vented to atmosphere through the aspiration vent, and when the aspirate valve is closed, the outer cannula lumen is not vented to atmosphere through the aspiration vent; and an instrument set housing, an elongate outer cannula having an axial lumen, a proximal portion coupled to the instrument set housing, and a distal portion having a tissue receiving aperture in a side wall thereof in communication with the lumen, an elongate inner cannula disposed within the outer cannula lumen, an aspiration vent fluidly coupling the outer cannula lumen to atmosphere, and an aspirate valve interposed in the aspiration vent and configured such that, when the aspirate valve is open, the outer cannula lumen is vented to atmosphere through the aspiration vent, and when the aspirate valve is closed, the outer cannula lumen is not vented to atmosphere through the aspiration vent; and (b) an instrument drive unit removably coupled to the instrument set, the instrument drive unit comprising 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 during operation of the biopsy system, such that an open distal end (28, 30) of the inner cannula moves back and forth across the tissue receiving aperture to sever tissue extending there through, and an actuating member configured to selectively mechanically prevent the aspirate valve from closing. 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 during operation of the biopsy system, such that an open distal end (28, 30) of the inner cannula moves back and forth across the tissue receiving aperture to sever tissue extending there through, and an actuating member configured to selectively mechanically prevent the aspirate valve from closing.