OBJECTIVE The purpose of this study is to establish the difference in lung nodule volume between standard-dose contrast-enhanced and low-dose unenhanced CT. METHODS Twenty patients with known pulmonary metastases underwent three CT examinations on 1 day: two unenhanced low-dose (120 kVp and 30 mAs) and a standard-dose (120-140 kVp and 75-200 mAs) contrast-enhanced chest CT examinations. For nodules<1000 mm3, nodule volume was quantified using dedicated software from the CT manufacturer. Wilcoxon's signed rank tests were used for analysis of nodules≤200 mm3 and >200 mm3 (approximately diameter of 8 mm). RESULTS One hundred one nodules (n=69≤200 mm3) were analyzed in 15 of these subjects. Measured volume of nodules≤200 mm3 was systematically lower on both low-dose unenhanced CT examinations when compared with standard-dose contrast-enhanced CT (differences, 13.7% and 15.5%, respectively; p<0.0001), but nodule volume was not different between low-dose CT (median difference, 1.0%; p=0.10). Nodule volume was not systematically different between the protocols for nodules>200 mm3 (p>0.30). CONCLUSIONS For lung nodules≤200 mm3 (approximately 8 mm) the measured volume on low-dose unenhanced CT is significantly lower when compared with standard-dose contrast-enhanced CT. This effect is likely due to contrast administration rather than other imaging parameters, which should be taken into account in the follow-up of lung nodules because growth can remain undetected or doubling time underestimated.