Background: On December 31, 2019, the World Health Organization (WHO) warned of pneumonia of unknown etiology in Wuhan, China. Rapid and accurate diagnosis of COVID-19 is crucial for the control of epidemic. Methods: In order to introduce a diagnosis and increase COVID-19 testing capacity, on March 27, 2020, Department of Medical Microbiology, University Clinical Center of Serbia was reorganized in staff and equipment. We started with molecular and serological diagnostics, and months later with tests for detection of SARS-CoV-2 antigen (Ag-RDT). On May 22, 2020, mass molecular testing at the National Laboratory for molecular diagnostics "Fire Eye" was started. Several real-time PCR (RT-PCR) protocols were applied. BGI RT-PCR (BGI Group, Shenzhen, China) was used for mass testing. The External Quality Control (EQC) was conducted in July 2020 and September 2021 (ECDC), and in December 2020 (WHO). Results: During two pandemic years 2021 and 2022, in Section of Virology we performed: 5.921 RT-PCRs, 75.807 Ag-RDT for detection of viral antigens, 37.373 rapid tests for detection of IgM and IgG antibodies and 491.995 RT-PCR tests in "Fire Eye" Laboratory. The EQC results confirmed the top quality of our work. For determining Omicron subvariants BA.1 and BA.2, in February 2022 we introduced Vir SNIP SARS-CoV-2 Spike S371L S373P Kit (TIB Molbiol, Berlin, Germany). Conclusions: In response to the challenges of the COVID-19 pandemic from a Department that processed up to 1.400 RT-PCR analyzes per year, we became a Department that issue up to 3.400 samples per day with EQC-certified quality and reliability.