This article discusses certain key legal and regulatory issues related to saving and sending out tissues, slides, and tissue blocks. It provides an overview of legal and regulatory requirements related to (1) the retention of slides and tissue blocks; (2) the maintenance of privacy and confidentiality when sending out slides for second opinions, disease consensus meetings, state registry reporting, or research; and (3) the ownership of tissues, slides, and tissue blocks. State and federal law requires laboratories to retain slides and tissue blocks for as long as 20 years. Federal regulations allow indirect treatment providers, such as most pathologists, to send out slides, tissues, and tissue blocks (with identifiable health information) for payment, treatment, or health care operations purposes, and certain public health reporting purposes, without patient permission. These regulations require pathologists to obtain patient authorization or an Institutional Review Board-approved waiver of informed consent when using any identifiable patient health information for research purposes. Federal and state law related to the ownership of tissues, slides, and tissue blocks remains unsettled. This article advocates obtaining a patient’s informed consent to use the patient’s tissues in research and other nontreatment contexts in order to avoid ownership dilemmas.