Background: The importance of antinucleolar antibodies seen by indirect immunofluorescence on HEp-2 cells, although associated with systemic sclerosis (SSc), in unselected patients is unknown. Aims: To determine the true clinical significance of antinucleolar antibodies in an unselected patient population. Methods: Antinucleolar antibody (ANoA) positive samples were identified in the immunology laboratory during routine autoimmune screening tests; case notes were reviewed using a standard proforma. Results: 104 patients with ANoA were identified and ANoA+ samples were subclassified into homogeneous, clumpy and speckled antinucleolar types. SSc was evident in only two (1.8%) patients. Other connective tissue diseases were identified in 33 patients (32%); 22 patients (21%) had evidence of various malignancies. Both disordered liver function and anaemia were seen in 22 patients and were the commonest laboratory abnormalities. Conclusions: Neither the presence nor subtype of ANoA is specific for systemic sclerosis. Laboratory comments appended to results should reflect this fact.