Structural and metabolic imaging are fundamental for diagnosis, treatment and follow-up in oncology. Beyond the well-established diagnostic imaging applications, ultrasounds are currently emerging in the clinical practice as a noninvasive technology for therapy. Indeed, the sound waves can be used to increase the temperature inside the target solid tumors, leading to apoptosis or necrosis of neoplastic tissues. The Magnetic resonance-guided focused ultrasound surgery (MRgFUS) technology represents a valid application of this ultrasound property, mainly used in oncology and neurology. In this paper; patient safety during MRgFUS treatments was investigated by a series of experiments in a tissue-mimicking phantom and performing ex vivo skin samples, to promptly identify unwanted temperature rises. The acquired MR images, used to evaluate the temperature in the treated areas, were analyzed to compare classical proton resonance frequency (PRF) shift techniques and referenceless thermometry methods to accurately assess the temperature variations. We exploited radial basis function (RBF) neural networks for referenceless thermometry and compared the results against interferometric optical fiber measurements. The experimental measurements were obtained using a set of interferometric optical fibers aimed at quantifying temperature variations directly in the sonication areas. The temperature increases during the treatment were not accurately detected by MRI-based referenceless thermometry methods, and more sensitive measurement systems, such as optical fibers, would be required. In-depth studies about these aspects are needed to monitor temperature and improve safety during MRgFUS treatments.