Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is by definition a highly heterogeneous tumour, which significantly impacts its diagnosis. The aim of the study was to evaluate the diagnostic performance of imaging using computed tomography and/or magnetic resonance (MR) and biopsy for the diagnosis of cHCC-CCA. cHCC-CCA resected between December 2006 and April 2017 with available pre-operative imaging and tumour biopsy were retrospectively included. cHCC-CCA diagnosis was based on morphological and immunophenotypical features. A total of 21 cHCC-CCA were compared to 21 intrahepatic cholangiocarcinoma (iCCA) as controls. All biopsies were reviewed. Two radiologists reviewed the cases and classified tumours into four patterns (type 1 [progressive enhancement of the entire lesion, iCCA type], type 2 [arterial enhancement with washout, HCC type], type 3 [mixed pattern with combinations of 1, 2 and 4] and type 4 [atypical pattern, areas of arterial enhancement without washout and/or hypovascular]). The presence of a type 3 pattern at imaging had a 48% sensitivity and 81% specificity for cHCC-CCA diagnosis. The initial diagnosis performed on biopsy was cHCC-CCA in 8/21 patients (38%). After reviewing and including immunophenotypical markers, two more cases were diagnosed as cHCC-CCA (48% sensibility, 100% specificity). When either imaging or biopsy suggested the diagnosis of cHCC-CCA, the sensitivity and specificity were 60% and 82% respectively. We showed that a two-step strategy combining imaging as the first step and biopsy as the second step improved the diagnostic performance of cHCC-CCA. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.