Clinical and anatomical pathology services are increasingly utilizing cloud information technology (IT) solutions to meet growing requirements for storage, computation, and other IT services. Cloud IT solutions are often considered on the promise of low cost of entry, durability and reliability, scalability, and features that are typically out of reach for small- or mid-sized IT organizations. However, use of cloud-based IT infrastructure also brings additional security and privacy risks to organizations, as unfamiliarity, public networks, and complex feature sets contribute to an increased surface area for attacks. In this best-practices guide, we aim to help both managers and IT professionals in healthcare environments understand the requirements and risks when using cloud-based IT infrastructure within the laboratory environment. We will describe how technical, operational, and organizational best practices that can help mitigate security, privacy, and other risks associated with the use of could infrastructure; furthermore, we identify how these best practices fit into healthcare regulatory frameworks.Among organizational best practices, we identify the need for specific hiring requirements, relationships with parent IT groups, mechanisms for reviewing and auditing security practices, and sound practices for onboarding and offboarding employees. Then, we highlight selected specific operational security, account security, and auditing/logging best practices. Finally, we describe how individual cloud technologies have specific resource-level security features. We emphasize that laboratory directors, managers, and IT professionals must ensure that the fundamental organizational and process-based requirements are addressed first, to establish the groundwork for technical security solutions and successful implementation of cloud infrastructure.