In this directed case study, students assume the role of investigators for the Centers for Disease Control and Prevention (CDC) as they examine and compare different DNA sequences from human patients infected with SARS-CoV-2, the coronavirus that causes COVID-19. The case focuses on the evolution and spread of SARS-CoV-2 during the world pandemic by tracking changes in its genomic code. Students use freely available bioinformatics tools (NCBI, BLAST, Nextstrain) to analyze the relatedness of various coronavirus strains against a consensus SARS-CoV-2 genome. Students generate DNA sequence alignments with related sequences and explore a phylogenetic tree. Finally, students apply these tools to viral sequences obtained from infected “patients” to decipher where they contracted the virus. Through these activities, students learn about sequencing tools and technology, and how they can be applied to epidemiology. This case was developed for use in an introductory biology or genetics course but could be adapted for upper-level molecular biology or biochemistry courses.