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Background: The microbiological diagnosis of skin lesions related to COVID-19 is not well known., Objective: Perform a microbiological diagnosis in COVID19-related cutaneous manifestations., Methods: A cross-sectional study was performed with 64 patients with cutaneous manifestations associated with COVID-19 who underwent serological and nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2., Results: Out of the 64 patients, 6 patients had positive RT-PCR, with all of them developing SARS-CoV-2 IgG and 4 of them had positive IgM + IgA. Of the 58 patients with negative RT-PCR, 8 cases had positive IgM + IgA and only one of them had IgG seroconversion. Therefore, the infection was demonstrated in 7 cases (10.9%) and was doubtful in 7 other cases (10.9%) who presented negative RT-PCR and presence of IgA + IgM without subsequent seroconversion of IgG. Fifty patients (78.1%) had negative serological tests. The most frequent cutaneous pattern was pseudo-chilblain (48.4%) followed by maculo-papular pattern (26.6%), urticarial lesions (10.9%), vesicular eruptions (6.3%) and livedoid pattern (4.7%). The maculo-papular pattern showed the highest positivity in RT-PCR (3 cases; 17.6%) and serologies (4 cases; 23.5%). Skin lesions developed after the systemic symptoms in most patients (19 cases; 61.3%)., Conclusions: Microbiological confirmation tests may not be an effective diagnostic technique for COVID-related cutaneous manifestations or that attributed lesions are not related to COVID-19. Confounding factors such as adverse drug reaction, serological cross-reactions with other viruses, the low production of antibodies in asymptomatic or mild forms of COVID-19 or its rapid disappearance, increase diagnostic uncertainty., (© 2021 Wiley Periodicals LLC.)