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(1) Background: In the current clinical practice of the COVID-19 infection, the focus should not be placed on the positive RT-PCR results, but rather on the epidemiological, clinical, and imaging aspects specific to the disease. (2) Case Report: We present the case of a 34-year-old female, who had contacts with both her parents, both of whom were confirmed to have SARS-CoV-2 infection by RT-PCR testing. She presented for about one week symptoms suggestive of COVID-19 infection, determining her to repeatedly go to the emergency room, where she had three negative SARS-CoV-2 RT-PCR tests. The blood tests revealed leukopenia with lymphocytopenia, with increased lactate dehydrogenase (LDH) and C-reactive protein (CRP). Moreover, the chest X-ray showed modifications specific for COVID-19, and the diagnosis of COVID-19 was set. Drug treatment with hydroxychloroquine, azithromycin, cephalosporins, systemic corticosteroids, anticoagulants, bronchodilators, and interleukin-6 inhibitors was initiated, together with oxygen therapy. (3) Discussion: SARS-CoV-2 RT-PCR testing may give false negative results due to inadequate biological sampling, or to the accuracy of the test methods. A significant contribution to the diagnosis is made by the specific computed tomography (CT) criteria of COVID-19. (4) Conclusions: A priority for COVID-19 diagnosis accuracy is epidemiological investigation, together with clinical criteria and CT imaging, even in the presence of a negative RT-PCR test.