The oligodendroglioma has been considered to be a tumour showing oligodendrocyte differentiation, but studies of the expression of oligodendrocyte markers have not conclusively demonstrated this and the pattern of differentiation of this tumour remains uncertain. Recent studies have suggested that some oligodendrogliomas may show neuronal differentiation. The aim of this study was to determine whether there was evidence of neuronal differentiation in a series of oligodendrogliomas, and, if so, to determine whether this identified a biologically or clinically distinct group. Immunohistochemistry was carried out on paraffin sections using antibodies to synaptophysin, phosphorylated and non-phosphorylated neurofilament proteins. An archival series of 32 oligodendrogliomas had been previously characterized for histological features, histological grade, Ki-67 labelling index, apoptosis index and prognosis. Six per cent of tumours showed expression of synaptophysin. Thirty-one per cent of cases showed expression of neurofilament proteins with an antibody to non-phosphorylated epitopes, but no cases were positive with antibodies to phosphorylated neurofilament epitopes. Tumours showing expression of neuronal markers did not show a difference in the distribution of histological grade or GFAP expression from those which did not express these markers, and there was no difference in labelling indices or prognosis between the two groups. In conclusion, a subset of oligodendrogliomas showed expression of neuronal lineage markers; this is discussed in relation to histogenesis and differential diagnosis. The expression of such markers did not identify a biologically or clinically distinct subgroup.