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Background and Aim Peliosis hepatis-like blood-filled cavities are frequently observed in hepatocellular carcinoma ( HCC). Peliotic change ( PC) is commonly seen in moderately differentiated HCCs and rarely in well-differentiated HCCs. We conducted clinicopathological analysis of well-differentiated HCC with PC ( PHCC). Methods A total of 1225 patients underwent hepatectomy at Kurume University Hospital between 1992 and 2010. Of these, 101 cases were diagnosed as well-differentiated HCC. Immunohistochemical double staining of CD34 and α smooth muscle actin was performed to examine the number and diameter of arterial blood vessels and drainage veins around tumors. We compared the clinical manifestations, histopathological features, and imaging findings of these cases. Results Seven cases of 101 well-differentiated HCCs had PC. Almost of PHCCs were macroscopically classified as the simple nodular type with a fibrous capsule, and microscopically showed thin trabecular arrangement of tumor cells and extensive dilated sinusoid-like structures filled with red blood cells. The number of arteries inside the tumor was significantly higher in PHCCs than in the simple nodular type of well-differentiated HCCs without PC. Furthermore, no significant differences were observed in the ratio of the number of irregularly shaped drainage veins around the tumor to the tumor diameter. Imaging revealed that most of the tumors had capsule-like structures and showed prolonged enhancement in the delayed phase of dynamic study of imagings. Conclusion PC is unusually observed in well-differentiated HCC and the size of PHCC was larger than that of well-differentiated HCC without PC and most are detected as a hypervascular tumor on images. [ABSTRACT FROM AUTHOR]