Lymphoma consists of a heterogeneous group of hematopoietic malignancies that is comprised of many different histologically and molecularly defined types and subtypes. Many of the non-Hodgkin’s lymphoma types defined in humans have histopathologically equivalent diseases occurring in dogs, thus providing an opportunity to study and conduct clinical trials in pet dogs with lymphoma to investigate new therapies, diagnostics, and devices to improve lymphoma patient outcomes. This chapter focuses on lymphoma types that are seen most frequently in dogs and are thus of the most comparative relevance. These include the aggressive lymphomas, which account for the greater proportion of canine lymphomas, including diffuse large B-cell lymphoma and peripheral T-cell lymphoma not otherwise specified and indolent lymphomas which are proportionally more common in humans and where in dogs marginal zone lymphoma, T-zone lymphoma, and cutaneous lymphoma are most frequent. Human and canine lymphomas overlap in their molecular and genetic basis, with different types and subtypes sharing varying degrees of common gene mutations and common dysregulation of signaling pathways. As such, spontaneous lymphoma in pet dogs is increasingly being used in the preclinical development of new lymphoma treatments, and published translational trials are briefly reviewed here. This chapter reviews the more relevant comparative aspects of human and canine lymphoma of interest to the veterinary and physician oncologist for the respective comparative species.