Marginal zone lymphoma (MZL) comprises approximately 7% of all mature non-Hodgkin lymphomas (NHLs) (Cerhan & Haberman, 2021). According to the World Health Organization classification, there are three subtypes: extranodal MZL, also referred to as mucosa-associated lymphatic tissue (MALT) lymphoma; splenic MZL, which originates from memory B lymphocytes located in the marginal zone of secondary lymphoid follicles present in the spleen; and nodal MZL, which originates in the lymph nodes (Swerdlow, 2017). Diagnosis and treatment for marginal zone lymphoma can be challenging for practitioners because it is relatively rare and can mimic the features of other hematologic malignancies, leading to delays in diagnosis and confusion about the best treatment strategy (NCCN, 2022). Additionally, a standard of care for MZL is not well established, making optimal treatment selection a challenge. In this activity, Ariela Noy, MD, and Matthew Matasar, MD, of Memorial Sloan Kettering Cancer Center will explore how to determine when MZL treatment should be initiated and will discuss the latest research on therapeutic strategies and their application in the clinic.