Asioli S, Zoli M, Guaraldi F, et al. - Six cases (4 F) of skull base dedifferentiated chordomas, treated surgically were recognized in order to better describe typical pathological, radiological and clinical characteristics, and to recognize possible genetic alterations responsible for tumor dedifferentiation. Following radiation therapy, transformation to dedifferentiated chordomas happened in three cases, two during tumor progression, while one was de-novo. MRI and surgical examination exhibited the presence of two distinct tumor components, correlated to the conventional and dedifferentiated part at histological examination. A PIK3CA mutation was shown by the de novo case. DNA methylation analysis exhibited constant epigenetic alterations in TERT, MAGEA11 and UXT. Since five out of six individuals died following surgery and radiation therapy, with a mean overall survival of 29 months, prognosis was poor. In summary, skull base dedifferentiated chordomas are exceptionally rare and aggressive neoplasms with typical MRI, surgical and histological peculiarities. Hence, an early and exact histological diagnosis is of chief significance. Moreover, in order to describe mechanisms involved in tumor dedifferentiation, molecular analysis seems promising.