Summary During the course of colon-rectum tumours a number of clinical events may occur in which conventional cytopathology can provide only a partial contribution to the definition of a differential diagnosis, i.e. effusions, distant recurrences and second neoplasias. In the present study we have evaluated whether monoclonal antibody (MoAb) D612, recognising a colon-rectum associated antigen, can be used in this context. To this end, MoAb D612 was employed in combination with a panel of MoAb of well defined tumour specificity in immunocytochemical tests. The immunocytochemical findings obtained were compared with the histological and clinical diagnosis. Of 62 effusions and 40 fine needle aspirates studied, MoAb D612 reactivity correlated with the correct diagnosis in 92.8% of the instances. These results indicate that this reagent may help to improve the current cytopathological diagnosis of colon-rectum tumours by identifying the colonic origin of metastases in patients with unknown primary tumour, differentiating ovarian carcinoma from colon metastases to the ovaries and establishing the presence of a second neoplasia in patients with a previous history other than colon carcinoma.