Introduction: We report on the first documented cluster of Coronavirus Disease 2019 cases amongst diagnostic laboratory staff and outline some of the initial and ongoing steps that are being implemented to manage and prevent the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in our laboratory. Case presentation: On 24 April 2020, three staff members of a tertiary diagnostic laboratory in Groote Schuur Hospital, Cape Town, South Africa, tested positive for SARS-CoV-2. Within seven days, a further nine cases were identified, which suggested an outbreak and prompted a full investigation. Management and outcome: A multifaceted strategic approach was adopted to halt the spread of SARS-CoV-2 in our laboratory. Interventions focused on simultaneously establishing appropriate risk mitigation and stratification strategies through the upscaling of infection prevention and control measures, whilst minimising disruption to service delivery. Conclusion: Laboratory Coronavirus Disease 2019 outbreaks have the potential to cripple a laboratory's testing capacity. Contingency planning and risk assessments should occur early, and interventions should be modified according to each laboratory's available resources and infrastructure.