Significant efforts invested in unmanned air vehicle (UAV) technology lead to a wide variety of new applications such as aero-photography and surveillance (Kontogiannis et al., 2013) and the operation of remotely piloted aircraft system (RPAS) undoubtedly has a great impact on the aviation industry and on the industrial applications. Experiments for measuring plume ash gas composition in the Stromboli Vulcan with a drone, inspections on wind turbine farms, high voltage lines and on antennae for the mobile connectivity, underline how the drones may be useful in case of disasters for analysis and for industrial applications. Unfortunately, the still incomplete regulatory framework and the frequency with which RPAS operate in urban areas or in unsegregated airspace highlight the many risks and the potentially catastrophes in case of risk underestimation and human errors. The European Aeronautic Safety Agency (EASA) is working together with the Joint Authorities for Rulemaking on Unmanned System (JARUS) work group for Safety & Risk Management to analyse and review the different strategies for safety assessment and human factors. The "just culture" approach may not be sufficient to avoid responsibilities in case of an air or ground collision and dramatic accidents. Exploring cases of near mid-air collisions between RPAS and commercial aircrafts, the paper firstly outlines and discusses the correlation between safety and knowledge through a survey conducted until the end of 2015 to assess the background of more than 1000 future RPAS pilots. Finally, examining the precarious situation when an incomplete preliminary risk assessment is conducted, the research work highlights how the human factor may affect the risks deriving from unsuitable selection of aircraft, airspace and weather conditions associated with the operator's lack of knowledge.