Molecular techniques (left) and experimental models (right) to study tumor heterogeneity in hepatocellular carcinoma (HCC) are shown. On the left, extracts from the tumor or liquid biopsy can be used to perform single-cell sequencing, spatial transcriptomics and multiplex proteomics, and flow and mass cytometry. On the right, multi-region samples from tumors can be used to establish primary cell lines, organoids, and patient-derived xenografts in immunocompromised mice.