The true incidence of hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) remains undetermined due to limited epidemiological studies and some conflicting results. Some studies indicated that in PBC, male gender, cirrhosis, hepatitis C virus (HCV) superinfection, and history of blood transfusion are associated with the development of HCC, and the occurrence of HCC in the early stage of PBC is rare. We present herein a 75-year-old male patient with stage I PBC who developed oropharyngeal squamous cell carcinoma, followed by HCC and duodenal adenocarcinoma without hepatitis B or C virus infection. While it could be argued that the concurrence of HCC and stage I-PBC in our patient was coincidental, patients with early stage PBC should be strictly followed up as cirrhotic patients with PBC by monitoring the serum concentration of tumor markers for HCC and appropriate imaging methods.