BACKGROUND: Experience in the use of whole slide imaging (WSI) for primary diagnosis is limited and there are no comprehensive reports evaluating this technology in liver biopsy specimens. AIMS: To determine the accuracy of interpretation of WSI compared with conventional light microscopy (CLM) in the diagnosis of needle liver biopsies. METHODS: Two experienced liver pathologists blindly analyzed 176 consecutive biopsies from the Pathology Department at the Hospital Clinic of Barcelona. One of the observers performed the initial evaluation with CLM, and the second evaluation with WSI, whereas the second observer performed the first evaluation with WSI and the second with CLM. All slides were digitized in a Ventana iScan HT at 400x and evaluated with the Virtuoso viewer (Roche diagnostics). We used kappa statistics (kappa) for two observations. RESULTS: Intra-observer agreement between WSI and CLM evaluations was almost perfect (96.6%, kappa=0.9; 95% confidence interval [95% CI]: 0.9-1 for observer 1, and 90.3%, kappa=0.9; 95%CI: 0.8-0.9 for observer 2). Both native and transplantation biopsies showed an almost perfect concordance in the diagnosis. CONCLUSION: Diagnosis of needle liver biopsy specimens using WSI is accurate. This technology can reliably be introduced in routine diagnosis.