During the past 15 years, a growing body of evidence incriminates hepatitis B virus as the major factor in the etiology of primary liver cancer. Epidemiological studies throughout the world reported a striking correspondence between areas where the frequency of primary liver cancer is high and where HBV infection is hyperendemic. Moreover, primary liver cancer is commonly associated with cirrhosis of the postnecrotic macronodular type. Such data suggested a sequence hepatitis-cirrhosis-PLC. Such sequence was confirmed by extensive serologic testing studies which reported a high frequency of HBV markers in PLC patients compared to matched control groups. Data collected in Senegal, Mali and Burundi on 12,000 individuals stress the importance of HBV infections in these countries, as the high rate of chronic carrier state in patients suffering from liver cirrhosis or primary liver cancer (62-63%) compared to the general population (12-17%). Other HBV markers including anti-HBs, anti-HBc, HBeAg and anti-HBe had no prognostic value in the sequence hepatitis-cirrhosis-PLC. A new HBV seric marker, the HBsAg/IgM complexes, observed in HBsAg positive individuals, is more frequently detected in PLC patients (50%) and cirrhosis (40%) than in healthy HBsAg carriers (14%). These results would indicate that HBsAg carriers are more likely to develop cirrhosis or primary liver cancer when they evidence HBsAg/IgM complexes. In conclusion, the seric markers of evolution towards primary liver cancer are: HBsAg (the highest known risk factor), the presence in such individuals of HBsAg/IgM complexes, and increased values of alphafoetoprotein.