Hepatocellular carcinoma (HCC) is one of the top-ranking cancers worldwide and in Southeast Asia. The high propensity for tumor recurrence, distant metastasis and chemoresistance remain major hurdles in the treatment of HCC. With advances on genetics and genomics research, molecular targeted therapies are emerging as a hope for better disease control. On the histological perspective, microscopic review of clinical samples has led to subclassification of HCC and establishment of new entities. In this review, latest understanding on macrotrabecular-massive HCC, steatohepatitic HCC, lymphocyte-rich HCC, scirrhous HCC, fibrolamellar carcinoma and combined hepatocellular-cholangiocarcinoma will be discussed, emphasizing on the clinical relevance of these pathological entities. Further delineation of the histological, immunohistochemical, molecular and biological phenotypes of primary liver cancer would to further enhance an integrated morphological-molecular classification that better predicts clinical outcome and guides clinical management.