To determine whether characteristics of focal hepatic parenchymal perfusion defects detected with computed tomographic arterial portography (CTAP) correlate with underlying pathologic processes, 245 perfusion defects detected with CTAP in 60 patients who subsequently underwent definitive hepatic surgery were characterized by shape, location within the liver, and relative attenuation value and were prospectively correlated with sectioned pathologic specimens. Of 177 round perfusion defects, 102 (58%) were malignant and 75 (42%) were benign. Only one (2%) of 53 peripheral wedge-shaped defects was malignant. All 15 peripheral flat defects were benign. Defects in characteristic locations anterior to the porta hepatis (n = 15) and adjacent to the intersegmental fissure (n = 7) were uniformly benign. While 83 (56%) of 147 soft-tissue attenuation defects were malignant, only four (6%) of 68 intermediate-attenuation defects were malignant. Although these characteristics of parenchymal perfusion defects aid in differentiation of benign from malignant processes, all other types of perfusion defects are nonspecific and may require biopsy.