Introduction: A glioblastoma is an intra-axial brain tumour of glial origin that belongs to the category of diffuse gliomas and is the most common malignant neoplasia of the central nervous system. The rate of survival at 5 years, from the moment of diagnosis, is not higher than 10%. Materials and methods: In this retrospective study, fifty-four patients diagnosed with glioblastoma, from the Pathology Department of the County Emergency Clinical Hospital of Târgu Mureș, between 2014 and 2017 were included. We studied the clinico-pathological data (age, gender, location, and laterality) and, respectively, the immunoexpression of p53, Ki67, ATRX, and IDH-1 proteins. Results: We observed a statistically significant association between the laterality of the tumour according to the age groups, with the localization on the right side being more frequent in the age group below 65 years of age, while the involvement of the left hemisphere was more prevalent in those over 65 years. Out of the total 54 cases, 87.04% were found to be primary glioblastomas; more than 70% of the cases were ATRX immunopositive; almost 80% of the glioblastomas studied had wild-type p53 profile; and 35% of the cases were found to have a Ki67 index greater than 20%. A statistically significant association between gender and ATRX mutation was found; female cases were ATRX immunopositive in 92% of the cases. Almost 70% of the cases were both IDH-1 and p53 wild-type, and we observed the presence of both mutations in only 3.7% of the cases. Approximately 83% of primary glioblastomas were ATRX positive, respectively, and all IDH-1 mutant cases were ATRX negative. Conclusions: Glioblastomas still represent a multidisciplinary challenge considering their reserved prognosis. In this study, we described the most common clinico-pathological characteristics and IHC marker expression profiles, highlighting a variety of percentage ranges in primary and secondary glioblastomas. Given the small number of studied cases, further prospective studies on larger cohorts are needed in the future to evaluate the role of these immunohistochemical markers as prognostic factors for survival or recurrence.