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Abstract The skull vault, formed by the flat bones of the skull, has a limited spectrum of disease that lies between the fields of neuro- and musculoskeletal radiology. Its unique abnormalities, as well as other ubiquitous ones, present particular features in this location. Moreover, some benign entities in this region may mimic malignancy if analyzed using classical bone-tumor criteria, and proper patient management requires being familiar with these presentations. This article is structured as a practical review offering a systematic diagnostic approach to focal calvarial lesions, broadly organized into four categories: (1) pseudolesions: arachnoid granulations, meningo-/encephaloceles, vascular canals, frontal hyperostosis, parietal thinning, parietal foramina, and sinus pericrani; (2) lytic: fibrous dysplasia, epidermal inclusion and dermoid cysts, eosinophilic granuloma, hemangioma, aneurysmal bone cyst, giant cell tumor, metastasis, and myeloma; (3) sclerotic: osteomas, osteosarcoma, and metastasis; (4) transdiploic: meningioma, hemangiopericytoma, lymphoma, and metastasis, along with other less common entities. Tips on the potential usefulness of functional imaging techniques such as MR dynamic susceptibility (T2*) perfusion, MR spectroscopy, diffusion-weighted imaging, and PET imaging are provided.