Given the ongoing pandemic, there is a need to identify SARS-CoV-2 and differentiate it from other respiratory viral infections in various critical settings. Since its introduction, rapid antigen testing is spreading worldwide, but diagnostic accuracy is extremely variable and often in disagreement with the manufacturer’s specifications. Our study compared the clinical performances of two microfluidic rapid antigen tests towards a molecular assay, starting from positive samples. A total of 151 swabs collected at the Microbiology and Virology Laboratory of A.O. “SS Antonio e Biagio e C. Arrigo” (Alessandria, Italy) for the diagnosis of SARS-CoV-2 were simultaneously tested to evaluate accuracy, specificity, and agreement with the RT-qPCR results. Both assays showed an overall agreement of 100% for negative specimens, while positive accuracy comprised between 45.10% and 54.90%. According to the manufacturer’s instructions, the greatest correlation between the antigenic and molecular assays was observed for the subset with high viral load (18/19, 94.74%), while it dramatically decreased for other subsets. Moreover, the ability to differentiate between SARS-CoV-2 and Flu provides an added value and could be addressed in an epidemic context. However, an in-house validation should be performed due to differences observed in performance declared by manufacturers and those actually obtained.