Changes in bone marrow cellularity can be an indicator of systemic toxicity and, therefore, bone marrow should be included in the battery of tissues examined for enhanced histopathology. However, the majority of changes in the bone marrow that are observed in toxicology studies are a response to hematological changes or lesions elsewhere in the body. For this reason, a consideration of all tissue changes in the body is required in order to differentiate toxic effects versus physiological responses in the bone marrow. While enhanced histopathology involves evaluation of the separate compartments in each lymphoid organ using descriptive rather than interpretive terminology, bone marrow is unique in that it lacks specific compartments. Furthermore, identification of erythroid, myeloid, megakaryocytic, and stromal cells, plus adipose tissue and hemosiderin-laden macrophages, can be accomplished from conventional H&E-stained sections, but conclusive identification of lymphoid lineage cells is not likely. This limits the extent of initial enhanced histopathology on bone marrow and argues for the use of cytological preparations for more comprehensive assessment of potential immunomodulatory effects.