Background: Glioblastoma with primitive neuronal components (GB/PNC) is an extremely rare type of glioblastoma characterized by presenting histological and cytogenetic features of both entities. The mixed nature of these tumors limits the imaging diagnosis and supposes a therapeutic dilemma. Case Description: We present the case of a 77-year-old female with a GB/PNC who is treated with surgery and adjuvant radiochemotherapy according to the STUPP protocol, where an abnormal uptake of 5-aminolevulinic acid (5-ALA) is evident during surgery in probable relation to the mixed nature of GB/PNC. Conclusion: GB/PNC is extremely rare tumors. Given its low prevalence, there are no studies that refer to the macroscopic characteristics of the tumor as well as evidence of the effectiveness of adjuvant treatment. Fluorescence-guided resection with 5-ALA is the surgical treatment of choice in surgery for high-grade gliomas; however, in GB/PNC, it may not be as useful since PNC may have less fluorescent marker uptake and be more dimly visualized when excited by light using the surgical microscope.