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Dispersion of a radiological source is a complex scenario in terms of first response, especially when it occurs in an urban environment. The authors in this paper designed, simulated, and analyzed the data from two different scenarios with the two perspectives of an unintentional fire event and a Radiological Dispersal Device (RDD) intentional explosion. The data of the simulated urban scenario are taken from a real case of orphan sources abandoned in a garage in the center of the city of Milan (Italy) in 2012. The dispersion and dose levels are simulated using Parallel Micro Swift Spray (PMSS) software, which takes into account the topographic and meteorological information of the reference scenarios. Apart from some differences in the response system of the two scenarios analyzed, the information provided by the modeling technique used, compared to other models not able to capture the actual urban and meteorological contexts, make it possible to modulate a response system that adheres to the real impact of the scenario. The authors, based on the model results and on the evidence provided by the case study, determine the various countermeasures to adopt to mitigate the impact for the population and to reduce the risk factors for the first responders.