A tissue removal device (100; 100'; 100") for acquiring one or more samples of intrauterine tissue from a patient, the tissue removal device (100; 100'; 100") comprising: a housing (102; 102'; 102"); an outer tube (108; 108'; 108") having a distal portion configured for transcervical insertion into a uterus, the outer tube (108; 108'; 108") having an outer tube lumen (148; 148'), a tissue in-take opening (114; 114') proximate a distal end (112; 112') thereof, and a proximal end (110; 110') coupled to the housing (102; 102'; 102"); an inner tube (118; 118'; 118") slidably disposed within the outer tube lumen (148; 148'), the inner tube (118; 118'; 118") having an inner tube lumen (150; 150') extending from an open inner tube distal end (122; 122') to an open inner tube proximal end (120; 120'), the open inner tube distal end (122; 122') comprising a cutting edge (124; 124') configured to sever intrauterine tissue extending through the tissue in-take opening (114; 114') in the outer tube (108; 108'; 108"); a vacuum generation chamber (138; 138') disposed within the housing (102; 102'; 102"); a movable piston (136; 136') slidably disposed in the vacuum generation chamber (138; 138'), so that the piston (136; 136') forms a wall of the vacuum generation chamber (138; 138'), and a manual actuator moveably coupled to the housing and operatively coupled to the piston, wherein movement of the actuator relative to the housing causes movement of the piston within the vacuum generation chamber; and the tissue removal device further comprising a collection chamber; wherein the inner tube lumen (150; 150') is selectively placed in fluid communication with the vacuum generation chamber (138; 138') via a distal one-way valve (140; 140'), characterized by the distal one-way valve (140; 140') being oriented so that material located in the inner tube lumen (150; 150') may be aspirated from the inner tube lumen (150; 150') into the vacuum generation chamber (138; 138') in response to movement of the piston (136; 136') in a distal direction, while material in the vacuum generation chamber (138; 138') is prevented by the distal one-way valve (140; 140') from entering the inner lumen (150; 150'); and wherein the vacuum generation chamber (138; 138') is selectively placed in fluid communication with the collection chamber (142; 142') via a proximal one-way valve (144; 144'), the proximal one-way valve (144; 144') being oriented so that material located in the vacuum generation chamber (138; 138') may be expelled from the vacuum generation chamber (138; 138') into the collection chamber (142; 142') in response to movement of the piston (136; 136') in a proximal direction, while material in the collection chamber (142; 142') is prevented from entering the vacuum generation chamber (138; 138'). a housing (102; 102'; 102"); an outer tube (108; 108'; 108") having a distal portion configured for transcervical insertion into a uterus, the outer tube (108; 108'; 108") having an outer tube lumen (148; 148'), a tissue in-take opening (114; 114') proximate a distal end (112; 112') thereof, and a proximal end (110; 110') coupled to the housing (102; 102'; 102"); an inner tube (118; 118'; 118") slidably disposed within the outer tube lumen (148; 148'), the inner tube (118; 118'; 118") having an inner tube lumen (150; 150') extending from an open inner tube distal end (122; 122') to an open inner tube proximal end (120; 120'), the open inner tube distal end (122; 122') comprising a cutting edge (124; 124') configured to sever intrauterine tissue extending through the tissue in-take opening (114; 114') in the outer tube (108; 108'; 108"); a vacuum generation chamber (138; 138') disposed within the housing (102; 102'; 102"); a movable piston (136; 136') slidably disposed in the vacuum generation chamber (138; 138'), so that the piston (136; 136') forms a wall of the vacuum generation chamber (138; 138'), and a manual actuator moveably coupled to the housing and operatively coupled to the piston, wherein movement of the actuator relative to the housing causes movement of the piston within the vacuum generation chamber; and the tissue removal device further comprising a collection chamber; wherein the inner tube lumen (150; 150') is selectively placed in fluid communication with the vacuum generation chamber (138; 138') via a distal one-way valve (140; 140'), characterized by the distal one-way valve (140; 140') being oriented so that material located in the inner tube lumen (150; 150') may be aspirated from the inner tube lumen (150; 150') into the vacuum generation chamber (138; 138') in response to movement of the piston (136; 136') in a distal direction, while material in the vacuum generation chamber (138; 138') is prevented by the distal one-way valve (140; 140') from entering the inner lumen (150; 150'); and wherein the vacuum generation chamber (138; 138') is selectively placed in fluid communication with the collection chamber (142; 142') via a proximal one-way valve (144; 144'), the proximal one-way valve (144; 144') being oriented so that material located in the vacuum generation chamber (138; 138') may be expelled from the vacuum generation chamber (138; 138') into the collection chamber (142; 142') in response to movement of the piston (136; 136') in a proximal direction, while material in the collection chamber (142; 142') is prevented from entering the vacuum generation chamber (138; 138').