ABSTRACT Histological diagnosis of hepatocellular carcinoma (HCC) in biopsy and fine needle aspiration material can pose difficult problems. This is particularly so in the fibrolamellar variant of the tumour (FLHCC) which has biological features distinctly different from those of common HCC (CHCC). Expression of CD99, a membrane localised glycoprotein which is known to be a feature of diagnostic importance in several malignant neoplasms was looked for in immunohistochemical preparation of tissue material from 18 cases of HCC, 6 FLHCC and 12 CHCC accessioned in our department. Positive staining of variable degrees and intesity was observed in all 18 cases. Non-neoplastic hepatocytes, normal or others and all the 18 other cases of non-HCC cancers outside the liver or metastatic within the liver were negative. In some cases, mostly of FLHCC, a definitive diagnosis could be suggested on the basis of CD99 positivity. It is concluded that in cases of HCC, particularly in small specimens and in FLHCC, immunostaining for CD99 will be of significant help in diagnosis.