Introduction The observation of multiple lesions in a skull computed tomography (CT) scan is always cause for concern because of the frequent possibility of neoplastic etiology, although granulomatous, infectious, vascular, iatrogenic, demielinating, trauma, parasitic diseases, and strokes can produce a similar aspect on radiology. A wide range of non-neoplastic conditions can mimic a brain tumor, both clinically and radiologically, representing a potential pitfall for physicians involved in patient care. The study's goal is to alert specialists to the possibility of other neoplastic and nonneoplastic etiologies in the differential diagnosis of hypodense lesions in non-contrast. Methods We performed a literature review using PubMed, Medline, Science Direct, Embase, Clinical Trials, Ebsco, and Scielo. Articles were selected in the period of 1986 to 2015. Discussion Knowledge of various etiologies when with multiple lesions appear on computed tomography allows specialists to guide the diagnosis to appropriate treatment, avoiding the irradiation of non-neoplastic lesions and unnecessary surgeries. The most common lesions were the neoplasm (74% to 86%), especially gliomas, followed by infections (8% to 15%), and infarcts (0.6% to 6%), which represent nonneoplastic lesions.