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The occurrence of both melanoma and glioma was first suggested by the observation of a familial association between these conditions, which was later confirmed by the description of the melanoma–astrocytoma syndrome, an extremely rare, inherited affliction in which people have an increased risk of developing melanoma and nervous system tumors. Taking into consideration the common embryologic precursor, the neuroectoderm, it was hypothesized that this syndrome is associated with a genetic disorder. While some families with germline CDKN2A mutations are prone to develop just melanomas, others develop both melanomas and astrocytomas or even other nervous-system neoplasms. Herein, we report the case of a 63-year-old male patient with no personal or family history of malignancy who had primary melanoma followed by glioblastoma. Our case report suggests that the occurrence of both melanoma and glioblastoma is most likely not coincidental but instead linked to genetic mutations of common embryologic precursors or signaling pathways. [ABSTRACT FROM AUTHOR]