Background: HCV is now considered to be a pandemic as it affects at least 170 million people, or 3% of the worldwide population (Tran, 2008), with the highest prevalence occurring in Egypt as it accounts for over 15% of its population (Lemon et al., 2007). Hepatocellular carcinoma (HCC) is increasing worldwide, mainly due to its association with HCV infection. Egypt has a high incidence of HCC which is attributed to Egypt's unique risk factor profile (El-Zayadi et al., 2005).Objective: To evaluate the value of different cellular and intercellular parameters using computerized ultrastructural morphometric analysis and its relation to HCC development as well as the stages of HCV.Patients and methods: Twenty patients (13 male, 7 female) were enrolled in this pilot study. Of these patients, 15 had chronic HCV and 5 had HCC complicating HCV infection. Each specimen was divided into two pieces, separately fixed and processed for light and electron microscopic examination.Results: The malignant hepatocytes revealed significantly lower cellular parameters (cell area, perimeter and diameter) and significantly higher nucleocytoplasmic ratio and total nucleolar area versus the chronically infected hepatocytes by HCV. Conclusion: It can be suggested that computerized ultrastructural morphometry as ancillary diagnostic tool for early prediction of malignant transformation of HCV infected hepatocytes.