A computed tomography (CT) cut-off for differentiating neoplastic lesions (polyps/carcinoma) from normal colon in contrast-enhanced CT colonography (CTC) relating to the contrast phase and lesion size is determined. CT values of 64 colonic lesions (27 polyps <10 mm, 13 polyps > or =10 mm, 24 carcinomas) were determined by region-of-interest (ROI) measurements in 38 patients who underwent contrast-enhanced CTC. In addition, the height (H) of the colonic lesions was measured in CT. CT values were also measured in the aorta (A), superior mesenteric vein (V) and colonic wall. The contrast phase was defined by xA + (1-x)V using x as a weighting factor for describing the different contrast phases ranging from the pure arterial phase (x=1) over the intermediate phases (x=0.9-0.1) to the pure venous phase (x=0). The CT values of the lesions were correlated with their height (H), the different phases (xA+(1-x)V) and the ratio [xA+(I-x)V]/H. The CT cut-off was linearly adjusted to the imaged contrast phase and height of the lesion by the line y=m[xA+(1-x)V]H+y(0). The slope m was determined by linear regression in the correlation (lesion approximately [xA+(i-x)V]/H) and the Y-intercept y(0) by the minimal shift of the line needed to maximize the accuracy of separating the colonic wall from the lesions. The CT value of the lesions correlated best with the intermediate phase: 0.4A + 0.6V (r=0.8 for polyps > or =10 mm, r=0.6 for carcinomas, r=0.4 for polyps <10 mm). The accuracy in the differentiation between lesions and normal colonic wall increased with the height implemented as divisor, reached 91% and was obtained by the dynamic cut-off described by the formula: cut-off (A,V,H)=1.1 [0.4A+0.6V]/H+69.8. The CT value of colonic polyps or carcinomas can be increased extrinsically by scanning in the phase in which 0.4A + 0.6V reaches its maximum. Differentiating lesions from normal colon based on CT values is possible in contrast-enhanced CTC and improves when the cut-off is adjusted (normalized) to the contrast phase and lesion size.