The increasingly widespread use of computed tomography (CT) has increased the number of detected lung lesions, which are then subjected to needle biopsy to obtain histopathological diagnosis. Obtaining high-quality biopsy specimens is fundamental for diagnosis and biomolecular characterisation that guide therapy decision-making. In order to obtain samples with high diagnostic potential, fusion imaging techniques, such as fusion between positron emission tomography and CT, have been introduced to target the biopsy where there more viable neoplastic cells can be sampled. Nowadays, dual-layer spectral CT represents a novel technology enabling an increased tissue characterisation. In particular, Z-effective images, i.e., colour-coded images based on the effective atomic number of tissue components, provide a higher level of discrimination than usual imaged based on x-ray attenuation in Hounsfield units and offer the potential of a better tissue characterisation. Our hypothesis is based on the future use of data provided by spectral CT, in particular by Z-effective images, as a guide for appropriate biopsy sampling for histopathological and biomolecular characterisation in the era of patient tailored-therapy.