We propose critical considerations on the usefulness of CT, MRI, and fMRI imaging fusion for the treatment of skull base lesions evaluating 41 cases (24 meningiomas: six petroclival, seven clinoidal, four olfactory, two in the foramen magnum, two spheno-petro-clival, one in the planum sphenoidale, one in the posterior pyramid and one in the PCA; five acoustic schwannomas, three epidermoids, two pituitary adenomas, two craniopharingiomas, two posterior fossa aneurysms, one trigeminal schwannoma, one dermoid and one juvenile angiofibroma). Data were collected, fused, integrated and reconstructed by a dedicated Stealth-Station system for Neuronavigation. CT images were acquired on axial non-overlapping slices, 1–3 mm thick; MRI images were obtained with a 1.5 T system, same FOV and thickness. During surgery the Mean Fiducially Error measured at 6 cm depth and anatomical distortion due to CSF loss was evaluated. Neuronavigation was possible in all cases and successfully applied in preoperative planning and during surgical procedures. The Mean Fiducially Error at 6 cm was 1.7 mm. CSF loss during surgery produced modifications on planned anatomy in a mean value of 0.6 mm. In all cases, imaging fusion for pre and intra-operative neuronavigation provided great advantages in the choice of the best approach, placing of bone flap, correct definition of tumour boundaries and meningeal implant, relationship with functional areas, early identification and real-time correction of the surgical route with respect of deep normal or distorted anatomic or pathologic structures and their eventual encasement or involvement by the pathologic primary process. Neuronavigation appeared ideal for skull base meningiomas making surgical manoeuvres safer, more effective and less invasive. In skull base lesions, CSF loss appeared not significant due to the fact that posterior fossa structures are strictly connected to each other and to the bone, thus are poorly affected by surgical deliquoration. We propose the possible extension of imaging fusion technique with the aim of optimizing the target in radiotherapy for intracranial tumours.