Malignant histiocytosis (MH) is a progressive systemic neoplastic proliferation of morphologically atypical histiocytes, well characterised in humans and dogs but only recently identified in the cat. In all species, liver, lung, lymph nodes, spleen and bone marrow are infiltrated by atypical histiocytes, and the disease is rapidly fatal. The purpose of this study was to describe the clinical, histological, immunohistochemical and ultrastructural findings of MH in a cat, together with the diagnostic work-up and a list of differential diagnoses. Clinical evaluation included a complete blood-cell count, serum biochemistry, urinalysis, serology and ultrasound examination. The cat had clinical signs of depression, thinness, dehydration, pale mucous membranes and tachycardia. Abdominal ultrasonography revealed generalised splenomegaly and hepatomegaly. Necroscopy showed whitish nodules, randomly scattered throughout the parenchyma in the spleen and liver. The periportal lymph nodes were greatly enlarged and the cut surface was uniformly greyish-white and translucent. Histological examination revealed pleomorphic proliferation of large round tumour cells, with numerous phagocytic vacuoles containing erytrocytes, leukocytes and haemosiderin. By immunohistochemistry, positivity for lysozyme and α1-antitrypsin and a scattered positivity for Mac 387 were observed. Ultrastructural features of tumour cells included cytoplasmic lipid droplets, lysosomes and phagolysosomes. MH in the cat needs to be differentiated from diffuse granulomatous disease, non-Hodgkin’s lymphoma and Hodgkin’s-like disease. The morphological features of the tumour cells, combined with immunohistochemical and ultrastructural observation, are consistent with a diagnosis of MH in the cat.