Three-dimensional methods for quantifying pulmonary nodule volume at computed tomography (CT) and the effect of imaging variables were studied by using a realistic phantom. Two fixed-threshold methods, a partial-volume method (PVM) and a variable method, were used to calculate volumes of 40 plastic nodules (largest dimension, <5 mm: 20 nodules with solid attenuation and 20 with ground-glass attenuation) of known volume. Tube current times (20 and 120 mAs), reconstruction algorithms (high and low frequency), and nodule characteristics were studied. Higher precision was associated with use of a PVM with predetermined pure nodule attenuation, high-frequency algorithm, and diagnostic CT technique (120 mAs). A PVM is promising for volume quantification and follow-up of nodules.