This report describes six cases of feline large granular lymphocyte lymphoma identified by light microscopy on the basis of their characteristic azurophilic granulation in Giemsa-stained plastic sections and by electron microscopy on the basis of their typical granules. Although the granules of all the tumor cells were negative for peroxidase activity, they all demonstrated chloroacetate-esterase and acid phosphatase activity. All the tumors reacted with cross-reacting antibodies against the CD3 antigen (epsilon chain) and did not react with a cross-reacting monoclonal antibody directed against epitopes on cytoplasmic domains of the CD20 antigen. Three tumors had a positive reaction with a monoclonal human CD57-like antibody. This is highly suggestive of either a cytotoxic T cell or a natural killer cell origin of the neoplasias. In three cats, although other abdominal organs were affected to a variable extent, the main neoplastic lesions were localized in the gastrointestinal tract and the jejunal lymph nodes. In contrast, in the other three cats, organ involvement was more widespread, affecting the lung (two), myocardium (two), precardiac mediastinum (one), salivary gland (one), and spinal cord (one); in addition, leukemia was present in two of these cats. The data presented indicate that tumors made up of large granular lymphocytes occur more frequently in cats than previously assumed and that they share many characteristic features with specific subtypes of clonal disorders of large granular lymphocytes in humans.