During the pandemic our institute became an important hub for COVID-19 testing and sequencing. The genomic surveillance of SARS-CoV-2 is of crucial importance in order to identify and monitor the emergence and spread of new virus variants that are showing a higher transmissibility or disease severity. Controlling the circulation of variants of concern (VOCs) or variants of interest (VOIs) is critical for public health decisions. Our institute participates actively in the COROnet, the network of highly specialized laboratories to perform PCR-based molecular COVID-19 tests, and in the WGSnet, the network for SARS-CoV-2 sequencing. The library preparation for the sequencing is in part automated with the Hamilton Microlab STAR Liquid Handling System which is able to process up to 96 samples. Sequencing is performed with the NextSeq 500 or the NovaSeq 6000 instrument that can analyse up to 768 samples in only one sequencing run ensuring therefore an unprecedented high throughput. We modified the current Illumina COVIDSeq protocol to guarantee a shorter turnaround time for the library preparation and to decrease potential noise-contamination while maintaining high sensitivity and specificity (Donzelli, S. et al., 2022). Following the sequencing of the viral genomes, the bioinformatic analysis provides valuable insights into the genetic makeup of the virus, including the identification of mutations and the lineage assignment. The data generated from these efforts is shared globally through public databases, the GISAID’s EpiCoV database and the Italian SARS-CoV-2 genomic surveillance platform I-Co-Gen, allowing researchers and public health officials to make informed decisions about how to control the pandemic. From April 2021 to April 2023 our institute has sequenced and reported more than 5700 positive cases.